Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

OBJECTIVE: To prepare decellularized nerve grafts from alpha-1, 3-galactosyltransferase (GGTA1) gene-edited pigs and explore their biocompatibility for xenotransplantation. METHODS: The sciatic nerves from wild-type pigs and GGTA1 gene-edited pigs were obtained and underwent decellularization. The alpha-galactosidase (α-gal) content in the sciatic nerves of GGTA1 gene-edited pigs was detected by using IB4 fluorescence staining and ELISA method to verify the knockout status of the GGTA1 gene, and using human sciatic nerve as a control. HE staining and scanning electron microscopy observation were used to observe the structure of the nerve samples. Immunofluorescence staining and DNA content determination were used to evaluate the degree of decellularization of the nerve samples. Fourteen nude mice were taken, and subcutaneous capsules were prepared on both sides of the spine. Decellularized nerve samples of wild-type pigs ( n=7) and GGTA1 gene-edited pigs ( n=7) were randomly implanted in the subcutaneous capsules. Blood was drawn at 1, 3, 5, and 7 days after implantation to detect neutrophil counting. RESULTS: IB4 fluorescence staining and ELISA detection showed that GGTA1 gene was successfully knocked out in the nerves of GGTA1 gene-edited pigs. HE staining showed that the structure of the decellularized nerve from GGTA1 gene-edited pigs was well preserved; the nerve basement membrane tube structure was visible under scanning electron microscopy; no cell nuclei was observed, and the extracellular matrix components was retained in the nerve grafts by immunofluorescence staining; and the DNA content was significantly reduced when compared with the normal nerves ( P<0.05). In vivo experiments showed that the number of neutrophils in the two groups were similar at 1, 3, and 7 days after implantation, with no significant difference ( P>0.05); only at 5 days, the number of neutrophils was significantly lower in the GGTA1 gene-edited pigs than in the wild-type pigs ( P<0.05). CONCLUSION The decellularized nerve grafts from GGTA1 gene-edited pigs have well-preserved nerve structure, complete decellularization, retain the natural nerve basement membrane tube structure and components, and low immune response after xenotransplantation through in vitro experiments.
Animals ; Transplantation, Heterologous ; Galactosyltransferases/genetics* ; Sciatic Nerve/immunology* ; Swine ; Tissue Engineering/methods* ; Humans ; Graft Rejection/prevention & control* ; Gene Editing ; Mice ; Mice, Nude ; Heterografts/immunology* ; Animals, Genetically Modified ; Tissue Scaffolds ; Decellularized Extracellular Matrix

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

Zhuye Shigaotang is one of the 100 classic prescriptions published by the National Administration of Traditional Chinese Medicine. This study used the traceability method and bibliometrics method to analyze the main applicable syndromes， efficacy and meanings， modern disease spectrum， and other aspects of Zhuye Shigaotang， so as to further promote the research and development of this prescription. The results showed that Zhuye Shigaotang originated from the Treatise on Febrile Diseases， and its ingredients included Lophatheri Herba， Gypsum Fibrosum， Pinelliae Rhizoma， Ophiopogonis Radix， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， and Oryza sativa. The main applicable syndromes of Zhuye Shigaotang recorded in ancient books included heatstroke， cough and asthma， sores， sweat syndrome， hiccup， insomnia， malaria， headache， blood syndrome， nasosinusitis， laryngitis， etc.， involving diseases of internal medicine， surgery， gynecology， and pediatrics. Its pathogenesis was "incomplete residual heat， both Qi and Yin injuries， and stomach-Qi disharmony". The research found that Zhuye Shigaotang could also be used to treat acne， measles， and cholera， and it was especially suitable for the treatment at the later stage of epidemic diseases. Lophatheri Herba and Gypsum Fibrosum in the prescription could clear away heat and relieve vexation. Ginseng Radix et Rhizoma，Ophiopogonis Radix， Ginseng Radix et Rhizoma， and Oryza sativa could promote body fluid production and invigorate Qi. Pinelliae Rhizoma could harmonize the stomach and stop vomiting. The prescription had stable compatibility and had the effects of clearing away heat， relieving vexation， invigorating Qi， promoting body fluid production， and harmonizing the stomach. Zhuye Shigaotang was widely applied in modern clinical practices， with high application frequency in the digestive system， pediatric-related diseases， respiratory system， infectious diseases， circulatory system， and neuropsychiatric system. The specific symptoms included recurrent aphtha， hiccup， infantile pneumonia， infantile summer fever， unexplained fever， upper respiratory tract infection， epidemic hemorrhagic fever， and late measles.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.