ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

ObjectiveAutoimmune thyroiditis （AIT） is a complex and immune-mediated disorder， with no established treatment protocol. Both Western and traditional Chinese medicine （TCM） focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM， using a novel evaluation method. Additionally， it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models， using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM， and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization， iodine induction， heterologous thyroid antigen immunization， and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%， 60%， 54%， and 63%， with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common， with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory， meeting the surface and structural effectiveness criteria of Western medicine. However， there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine， with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine， creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM， providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Periodontitis patients are at risk of alveolar bone loss during orthodontic treatment. The aim of this study was to investigate whether intermittent parathyroid hormone (1-34) treatment (iPTH) could reduce alveolar bone loss during orthodontic tooth movement (OTM) in individuals with periodontitis and the underlying mechanism. A rat model of OTM in the context of periodontitis was established and alveolar bone loss was observed. The control, iPTH and iPTH + stattic groups received injections of vehicle, PTH and vehicle, or PTH and the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic, respectively. iPTH prevented alveolar bone loss by enhancing osteogenesis and suppressing bone resorption in the alveolar bone during OTM in rats with periodontitis. This effect of iPTH was along with STAT3 activation and reduced by a local injection of stattic. iPTH promoted osteoblastic differentiation and might further regulate the Wnt/β-catenin pathway in a STAT3-dependent manner. The findings of this study suggest that iPTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/β-catenin crosstalk.
Animals ; Homeostasis ; Humans ; Osteogenesis ; Parathyroid Hormone ; Periodontitis/drug therapy* ; Rats ; STAT3 Transcription Factor/metabolism* ; Tooth Movement Techniques ; beta Catenin