Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.

Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

BACKGROUND: The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs. METHODS: This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants' demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables. RESULTS: The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity ( r  = 0.516, P <0.01), whereas LPTA showed a strong negative correlation ( r  = -0.662, P <0.01). Additionally, SA ( r  = 0.616, P <0.05), and TT-TG showed a strong positive correlation ( r  = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = -2.946, P <0.001) and side (β = -0.839, P  = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = -0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = -0.326, P  = 0.041), body mass index (β = -0.061, P  = 0.017) and age (β = -0.025, P <0.001) was associated with TT-TG. CONCLUSION Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.
Humans ; Female ; Male ; Osteoarthritis, Knee/pathology* ; Middle Aged ; Retrospective Studies ; Aged ; Patellofemoral Joint/pathology* ; Magnetic Resonance Imaging ; Adult ; Patella/pathology* ; Radiography

This study summarized Professor Su Peiji's clinical experience in differenting and treating lumbago and leg pain.He contends that the disease involves the liver and kidney,manifesting as a syndrome of deficiency in origin and excess in superficiality,with liver-kidney deficiency and insufficiency of essence and blood as the root cause,and exogenous wind,cold,and dampness invading the meridians and then causing obstruction as the superficial manifestation.The principal pathological factors include wind,cold,dampness,blood stasis,and deficiency.In clinical practice,he follows the therapeutic principle of expelling pathogens and supporting healthy qi in accordance with the abundance or deficiency of pathogens and healthy qi,takes the therapy of tonifying the liver and kidney as the primary approach,and applies the adjuvant therapies of dispelling wind,cold,and dampness as well as relaxing tendons and activating collaterals.By incorporating the theory of collateral diseases,Professor Su Peiji proposes that the deficiency-excess of collateral diseases is closely related to the onset of lumbago and leg pain.His therapeutic approach centers around Shuji Formula,a self-formulated formula which is composed of Taxilli Herba,Achyranthis Bidentatae Radix,Stephaniae Tetrandrae Radix,Angelicae Pubescentis Radix,Clematidis Radix et Rhizoma,Aconiti Radix Cocta,Flemingiae Radix et Caulis,Millettiae Speciosae Radix,Poria,Angelicae Sinensis Radix,Paeoniae Radix Alba,Chuanxiong Rhizoma,Spatholobi Caulis,Tinosporae sinensis Caulis,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.Modified use of herbs was performed according to the predominance of wind,cold,dampness,blood stasis,or deficiency,so as to achieve the effects of tonifying the liver and kidney,strengthening bones and tendons,dispelling wind,cold and dampness,and relaxing tendons and activating collaterals.

Objective To investigate alterations in plasma complement levels and white matter imaging characteristics,along with their relationship in patients with first-episode schizophrenia(SCZ).Methods Thirty-eight patients with first-episode schizophrenia and 42 healthy controls were enrolled.Whole-brain diffusion tensor imaging(DTI)was performed using a Philips 3.0 T MRI scanner.Tract-based spatial statistics(TBSS)combined with the Johns Hopkins University(JHU)white matter labels atlas was used to extract and compare white matter characteristics between the two groups.Plasma levels of complement components(C1q,C3,C4,factor B,factor H,and factor P)were measured using the MILLIPLEX? human complement assay kit via multiplex analysis.Spearman correlation analysis was conducted to examine the association between plasma complement levels and white matter features.Results The radial diffusivity(RD)of the left fornix/stria terminalis was significantly higher in the patient group compared to the control group[(0.62±0.04)×10-3mm2/s vs.(0.60±0.03)×10-3mm2/s,PFDR=0.048)].Factor H[677.71(551.58,846.21)ng/mL vs.582.76(513.93,729.71)ng/mL,P=0.041]and factor P[71.36(57.30,95.99)ng/mL vs.60.08(46.67,80.03)ng/mL,P=0.011]were both significantly elevated compared to the control group.Moreover,RD values in the left fornix/stria terminalis were negatively correlated with plasma C3 levels in the patient group(r=-0.362,P=0.025).Conclusion Patients with first-episode schizophrenia exhibit white matter microstructural abnormalities in left fornix/stria terminalis,which are significantly associated with plasma complement levels.

Objective To investigate alterations in plasma complement levels and white matter imaging characteristics,along with their relationship in patients with first-episode schizophrenia(SCZ).Methods Thirty-eight patients with first-episode schizophrenia and 42 healthy controls were enrolled.Whole-brain diffusion tensor imaging(DTI)was performed using a Philips 3.0 T MRI scanner.Tract-based spatial statistics(TBSS)combined with the Johns Hopkins University(JHU)white matter labels atlas was used to extract and compare white matter characteristics between the two groups.Plasma levels of complement components(C1q,C3,C4,factor B,factor H,and factor P)were measured using the MILLIPLEX? human complement assay kit via multiplex analysis.Spearman correlation analysis was conducted to examine the association between plasma complement levels and white matter features.Results The radial diffusivity(RD)of the left fornix/stria terminalis was significantly higher in the patient group compared to the control group[(0.62±0.04)×10-3mm2/s vs.(0.60±0.03)×10-3mm2/s,PFDR=0.048)].Factor H[677.71(551.58,846.21)ng/mL vs.582.76(513.93,729.71)ng/mL,P=0.041]and factor P[71.36(57.30,95.99)ng/mL vs.60.08(46.67,80.03)ng/mL,P=0.011]were both significantly elevated compared to the control group.Moreover,RD values in the left fornix/stria terminalis were negatively correlated with plasma C3 levels in the patient group(r=-0.362,P=0.025).Conclusion Patients with first-episode schizophrenia exhibit white matter microstructural abnormalities in left fornix/stria terminalis,which are significantly associated with plasma complement levels.

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

【Objective】 To detect the anti-SARS-CoV-2 neutralizing antibody levels in convalescent plasma (CP) and to evaluate whether it has specific anti-SARS-CoV-2 S antigen effect, so as to provide laboratory data support for clinical use of CP. 【Methods】 Nine CP donors who have recovered from COVID-19 were studied, and 4 volunteers who completed the vaccination and 3 asymptomatic infected blood donors were compared. Anti-SARS-CoV-2 antibodies including total antibody, IgM and IgG were measured by chemiluminescence microparticle immunoassays (CMIA) test in three groups. The VSV pseudovirus-based neutralization assay for evaluating neutralizing antibodies against SARS-CoV-2 was carried out in all samples. 【Results】 All samples were tested positive by the total antibody and IgG CMIA in COVID-19 CP donors and recipients of inactivated COVID-19 vaccine. High titers of IgG were observed in CP donors and vaccine recipients compared with asymptomatic blood donors. All vaccine recipients and 8 of 9 CP donors tested positive by SARS-CoV-2 pseudovirus-based neutralization test, whereas all asymptomatic blood donors tested negative. 【Conclusion】 The levels and characteristics of neutralizing antibodies among COVID-19 CP donors, vaccine recipients and asymptomatic blood donors were different. When unable to implement the pseudovirus assay to measure neutralizing antibodies, the detection of total antibody can be considered instead.