Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

Mucinous adenocarcinoma of the renal pelvis is rare in clinical practice. This article reported a case of primary renal pelvis mucinous adenocarcinoma mixed with signet ring cell carcinoma. The patient was admitted to hospital due to right low back pain, and was diagnosed with right kidney stones accompanied by hydrops and infection, right kidney abscess, and nonfunctional right kidney after complete examination. Right renal puncture drainage was performed twice, followed by laparoscopic robot assisted right neprectomy. The postoperative pathological diagnosis was right renal pelvis primary mucinous adenocarcinoma (mixed with signet-ring cell carcinoma). Eleven months after the operation, regular "sodium folinate + oxaliplatin + 5-fluorouracil" chemotherapy was performed for 12 courses, and imaging showed no signs of recurrence or metastasis.

BACKGROUND:Scaffold materials serve as platforms that provide space and structure,playing a crucial role in the regeneration of cartilage tissue.Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE:To review the design principles and preparation methods of cartilage scaffolds,and to further explore the advantages and limitations of various preparation methods. METHODS:Literature searches were conducted on the databases of CNKI,WanFang Data,PubMed,and FMRS from 1998 to 2023.The search terms were"cartilage repair,cartilage tissue engineering,cartilage scaffold materials,preparation"in Chinese and English.A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION:(1)The articular cartilage has a unique structure and limited self-repair capacity after injury.Even if self-repair occurs,the newly formed cartilage is typically fibrocartilage,which is far inferior to normal articular cartilage in terms of structure and mechanical properties.It is difficult to maintain normal function and often leads to degenerative changes.Currently,the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects:biocompatibility and biodegradability,suitable pore structure and porosity,appropriate mechanical properties,and bioactivity.(2)Research on the preparation of cartilage scaffolds has made significant progress,continuously introducing new preparation methods and optimization strategies.These methods have their advantages and disadvantages,providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements.

BACKGROUND:Bone formation is the process by which osteoblasts synthesize and secrete osteoid and promote its mineralization,which generally involves mechanical signal transduction.Osteoblasts are primarily regulated by mechanical factors such as gravity,compressive stress,tensile stress,fluid shear stress,and hydrostatic pressure in vivo,and different mechanical stimuli modulate the proliferation,differentiation,and apoptosis of osteoblasts through various mechanisms,including hormones,cytoskeletal proteins,and microRNAs.By clarifying the effects of biomechanical forces on osteoblasts,it provides ideas and a reference basis for the treatment of osteometabolic diseases involving osteoblasts. OBJECTIVE:To review the effects of different biomechanical forces on the biological characteristics of osteoblasts. METHODS:We conducted a literature search using PubMed,Web of Science,FMRS,CNKI,and WanFang databases for relevant publications published from 2000 to 2023,covering basic research and tissue engineering studies related to the effects of biomechanical forces on osteoblasts.Ultimately,a total of 70 articles were reviewed. RESULTS AND CONCLUSION:Different biomechanical forces have an impact on the biological characteristics of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are dependent on the intensity and duration of the applied force.Specifically,the effects are as follows:(1)Under microgravity conditions,osteoblast proliferation and differentiation are inhibited,resulting in a decrease in bone density and the development of osteoporosis.(2)Compared to microgravity,hypergravity has a promoting effect on osteoblast proliferation.(3)The effects of compressive stress on osteoblasts are dependent on the loading intensity and time.Appropriate compressive stress can promote osteoblast proliferation and differentiation,which is beneficial for bone tissue formation and repair,while excessive compressive stress can cause osteoblast apoptosis and bone tissue destruction.(4)The biological effects of different types of tensile stress on osteoblasts differ.Studies have shown that a strain rate within the range of 0-12%has a promoting effect on osteoblast proliferation.(5)Fluid shear stress can promote osteoblast proliferation and differentiation and enhance the bone-inducing effect of biomaterials.(6)Static hydrostatic pressure can affect the biological behavior of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are closely related to the time and intensity of the pressure.Understanding the effects of different biomechanical forces on osteoblasts is of great significance for a deeper understanding of bone growth and maintenance mechanisms.

Objective To analyze the changing trends of the incidence and onset age of cervical cancer in Jiangsu Province by using cancer registration data from 2009 to 2019. Methods The information of national cancer registries with continuous data from 2009 to 2019 was selected, and the quality control indices of cancer registration must be up to standards. A total of 16 registries were included in this study. Statistical analysis indicators include the crude incidence rate of cervical cancer, age-standardized incidence rate, actual average onset age, age-standardized average onset age, and average annual percentage change (AAPC). A birth cohort model was constructed to analyze the incidence of cervical cancer among women born from 2009 to 2019 and its incidence trend. Results From 2009 to 2019, the crude and age-standardized incidence rates of cervical cancer among women in Jiangsu Province showed upward trends, with AAPCs of 5.62% (95%CI: 3.47−7.82) and 4.14% (95%CI: 2.06−6.27), respectively. The incidence rate of cervical cancer in rural areas (AAPC=4.46, 95%CI: 1.13−7.91) increased more than that in urban areas (AAPC=3.83, 95%CI: 2.81−4.86). The actual average onset age of cervical cancer increased from 51.53 years in 2009 to 55.07 years in 2019 (β=0.36, P<0.05). The age-standardized average onset age increased from 48.89 years in 2009 to 50.43 years in 2019 (β=0.21, P<0.05). The age composition ratios of cervical cancer in the age group of 60 years and older were 31.90% in 2019 and 22.40% in 2009 (β=3.66, P<0.05). The incidence of cervical cancer in the same age group of people with different birth years showed an upward trend with the increase in birth year. Conclusion From 2009 to 2019, the incidence rate of cervical cancer in Jiangsu Province showed an upward trend, and this trend was more obvious in rural areas than in urban areas. In addition, the average onset age of cervical cancer showed an upward trend.

Objective To analyze the type and incidence of abnormal chromosome karyotype in peripheral blood of infertile patients with different semen quality.Methods Selectet 292 infertility patients who came to our hospital from January 2018 to December 2021 for G-banding karyotyping and semen analysis.According to the semen analysis results,the patients were divided into abnormal semen quality group and normal control group.We made statistics and analysis on the abnormal karyotypes.Results In the group with abnormal semen quality,20 cases(18.87%)of abnormal karyotypes were found.In the normal control group,9 cases(4.84%)had abnormal karyotypes were found.The comparison of the abnormal rates of peripheral blood chromosome karyotypes between the two groups showed statistical significance(P<0.05).The detection rate of chromosomal abnormalities in patients with Azoospermia was 50%,and sex chromosome abnormalities were the main types of abnormalities in this group.Conclusion Karyotype analysis of infertile patients can effectively analyze the causes of infertility,and has important clinical significance for assisted reproduction and primary prevention of birth defects.

Objective To investigate the level of inflammation after interventional treatment in patients undergoing intracranial stent implantation by measuring the changes in the plasma levels of monocytes and high-density lipoprotein cholesterol（HDL-C） and monocyte to high-density lipoprotein cholesterol ratio （MHR） after stent implantation for intracranial atherosclerotic stenosis （ICAS） in high-altitude areas， as well as the causes of such changes and their value in predicting clinical prognosis. Methods The ICAS patients who were consecutively admitted to Qinghai Provincial People’s Hospital， from June 10， 2017 to March 1， 2022 and underwent interventional treatment were enrolled， and all patients signed the informed consent. Clinical data and the data on interventional surgery were collected， and blood samples were collected before interventional treatment， within 72 hours after interventional treatment， and at 3 months after interventional treatment to measure the levels of monocytes and HDL-C. The above indicators were compared before and after interventional treatment， and such changes were analyzed in terms of their association with the site of cerebrovascular stenosis and NIHSS score. Results A total of 123 patients with severe ICAS who underwent intracranial stent implantation and had complete data were included. Compared with the data before surgery， there was a significant increase in the plasma level of monocytes at 72 hours after stent implantation [（0.64±0.21）×109/L vs （0.53±0.17）×109/L， P<0.001]， while there was a significant reduction in the plasma level of monocytes at 3 months after stent implantation [（0.43±0.14）×109/L vs （0.53±0.17）×109/L，P<0.001]. Compared with the data before surgery， there was no significant change in HDL-C within 72 hours after surgery[（0.93±0.21）mmol/L vs （0.93±0.18）mmol/L， P>0.005]， while there was a significantly increase in HDL-C at 3 months after surgery[（1.05±0.21 mmol/L vs （0.93±0.18）mmol/L， P<0.001）. There was no significant correlation between monocytes/HDL-C/MHR and NIHSS score before surgery and at 72 hours after surgery （P>0.005）； there was no significant correlation between monocytes/HDL-C/MHR and NIHSS score before surgery and within 72 hours after surgery （P>0.005）；at 3 months after surgery， monocytes and MHR were significantly negatively correlated with NIHSS score （r=-0.271，P<0.05；r=-0.320，P<0.005），while HDL-C was significantly positively correlated with NIHSS score （r=0.213， P<0.001）. Conclusion Balloon dilatation and ischemia/reperfusion after intracranial stent implantation may cause inflammatory response in the body， thereby leading to increases in the level of monocytes and the value of MHR. Therefore， monocytes， HDL-C， and MHR may be used as predictive factors for the improvement in neurological defects in the convalescence stage after stent implantation.
Monocytes

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.
Glycolysis ; Colonic Neoplasms/metabolism* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Phosphopyruvate Hydratase/metabolism* ; Flavanones/pharmacology* ; Cell Line, Tumor ; Databases, Genetic ; Cell Proliferation/drug effects* ; Transfection ; Warburg Effect, Oncologic

OBJECTIVE To study the inhibitory effects and possible mechanism of naringenin on the activation of hepatic stellate cells. METHODS Using human hepatocytes LO2 as reference， based on drug intervention concentration screened by MTT assay， the effects of naringenin （Western blot assay and trypan blue staining test in 10， 20， 40 μmol/L， immunofluorescence assay in 40 μmol/L） on the expressions of liver fibrosis markers protein （collagen Ⅰ， α-SMA） and mRNA （α1-pro collagen Ⅰ， α-SMA） in human hepatic stellate cells LX2， and the expressions of cell apoptosis and apoptosis-related proteins （Bcl-2， Bax， cleaved caspase-3） were investigated. The apoptosis agents （Z-VAD-FMK， FMK）， ferroptosis pathway inhibitor ferrostatin-1， and programmed death pathway inhibitor necrostatin-1 were used to verify the mechanism of the above effects. RESULTS The naringenin could significantly down-regulate protein expressions of collagen Ⅰ （except for naringenin 10 μmol/L） and α-SMA， mRNA expressions of α1-pro collagen Ⅰ （except for naringenin 10 μmol/L） and α-SMA （P＜0.05）； it also induced LX2 cell apoptosis and increased its apoptotic ratio， down-regulated the protein expression of Bcl-2 while up-regulated the protein expressions of Bax （except for naringenin 10 μmol/L） and cleaved caspase-3 （except for naringenin 10 μmol/L）. FMK could reverse above effects of naringenin on LX2 cells （P＜0.05）. CONCLUSIONS Naringenin can inhibit the activation of hepatic stellate cells LX2 through activating the cell apoptosis signal， which plays ameliorative role in liver fibrosis.

OBJECTIVE To study the effects of cy cloastragenol （CAG） on carbon tetrachloride （CCl4）-induced hepatic fibrosis（HF）and glycolysis in mice. METHODS Male ICR mice were randomly divided into blank group ，model group ，CAG low-dose，medium-dose and high-dose groups （60，120，240 mg/kg），with 6 mice in each group. Except that blank group was given olive oil intraperitoneally ，the mice in other groups were intraperitoneally injected with 10％CCl4-olive oil solution （5 mL/kg） three times a week for 8 weeks to induce HF model. From the 4th week after modeling ，mice in each drug group were given corresponding drug solution intragastrically （10 mL/kg），and mice in blank group and model group were given 0.5％ sodium carboxymethyl cellulose solution intragastrically （10 mL/kg），once a day for 4 weeks. During the experiment ，the body weight of mice were weighted ；after last gastrogavage ，the liver weight was weighted and liver indexes of mice were calculated. The changes of hepatic injury indexes [aspartate aminotransferase （AST）， alanine aminotransferase （ALT）]， related indexes of HF [hematoxylin-eosin （HE）staining score ，Masson and Picrosirius red staining collagen volume fraction ，collagen Ⅰ，α-smooth muscle actin （α-SMA）] and related indexes of glycolysis [lactic acid （LD），hexokinase（HK），phosphofructokinase（PFK）， pyruvate kinase （PK）] were all detected. RESULTS Compared with model group ，the collagen deposition and fibrosis of mice in each drug group were reduced ，and the body weights of mice （except for CAG low-dose group ）were increased to some extent （P＜0.05）. Liver indexes ，serum levels of ALT and AST ，HE staining score of liver histopathology ，Masson and Picrosirius red staining collagen volume fraction ，protein expression of collagen Ⅰ and α-SMA，serum content of LD ，the levels of HK ，PFK and PK in serum and hepatic tissues （except for hepatic tissue of CAG low-dose group ）were all decreased significantly （P＜0.05）. CONCLUSIONS CAG can improve HF in mice induced by CCl 4，and reduce the levels of key enzymes and products of glycolysis.