Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Liver diseases have become a major challenge threating the global health, posing a heavy burden on both social and personal well-being. In recent years, the development of the gut-liver axis theory has provided new research perspectives and intervention strategies for the prevention and treatment of liver diseases. Natural products, recognized as biological molecules with diverse sources, rich activities, and minimal side effects, demonstrate great potential in regulating intestinal flora and improving liver health. Studies have shown that natural products such as saponins, polyphenols, polysaccharides, and alkaloids can regulate the composition and metabolites of intestinal flora, thereby intervening in liver diseases. In this paper, we systematically review the role of natural products in the regulation of the intestinal flora-gut-liver axis and summarize recent research progress in the prevention and treatment of liver diseases. Furthermore, we outline the challenges and limitations currently facing the study in this field. Finally, this paper makes an outlook on the clinical application of natural products in treating liver diseases and discusses future research directions, aiming to give new insights into the mechanisms by which natural products regulate the intestinal flora-gut-liver axis and the applications of these products in the prevention and treatment of liver diseases.
Humans ; Gastrointestinal Microbiome/drug effects* ; Liver Diseases/prevention & control* ; Biological Products/pharmacology* ; Polyphenols/pharmacology* ; Saponins/pharmacology* ; Intestines/microbiology* ; Alkaloids/pharmacology* ; Polysaccharides/pharmacology* ; Liver

Objective:To investigate the effect of different acquisition duration of brain image of 18F-florbetaben(18F-FBB)positron emission tomography(PET)on standardized uptake value(SUV).Methods:Eight subjects who underwent 18F-FBB PET examination in Chinese PLA General Hospital from May 2021 to June 2021 were selected,including 5 persons of healthy control and 3 patients with mild cognitive impairment(MCI).All subjects underwent 18F-FBB PET imaging,and the dynamic PET images of them on brains were continuously acquired for 20 min between 90 and 110 min after the 18F-FBB injection was injected as(3.7-5.5 MBq/kg).Under the situation that other reconstruction parameters did not change,the images were reconstructed at 0-1,0-3,0-5,0-10,0-15 and 0-20 min,respectively.The same of region of interest(ROI)ranges were delineated in bilateral frontal cortex,bilateral temporal cortex,bilateral parietal cortex,posterior cingulate gyrus and cerebellar cortex of each group of images.And then,the corresponding mean standardized uptake value(SUVmean)of each region was obtained.The differences of SUVmean values of different ROI values between each group of data images and the images of 0-20 min were compared and analyzed.Results:There were significant differences in SUVmean between the acquired images in 0-1,0-3,0-5 and 0-10 min and the acquired standard images of 0-20 min(t=-7.569--2.410,P<0.05),respectively.There were no significant differences in SUVmean between the acquired images of 0-15 min and the acquired standard images of 0-20 min in the bilateral frontal lobe,bilateral temporal lobe,bilateral parietal cortex and posterior cingulate gyrus(P>0.05),only there was significant difference in the cerebellar cortex area between them(t=-5.597,P<0.001).Conclusion:The results of 15 min can reach to the similar results of 20 min in acquiring images,which can shorten the time of examination,and enhance the degrees of comfort and cooperation of patients in examination.It has clinical application value.

Objective:To evaluate the potential of 177Lu-prostate specific membrane antigen (PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and compare it with 177Lu-PSMA-I&T. Methods:177Lu-PSMA-3Q was prepared and the quality control and stability testing were performed. Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were conducted in normal BALB/c mice and 22Rv1 tumor-bearing mice. SPECT imaging was performed on 2 patients (60 and 76 years old) with mCRPC from Chinese PLA General Hospital at 24, 72, and 120 h after injection of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T ((7.40±0.74) GBq). Data were analyzed by using independent-sample t test. Results:177Lu-PSMA-3Q was prepared with the total activity of 74 GBq, the yield rate of 95% (uncorrected), and the radiochemical purity was still above 95% after 168 h at room temperature. The distribution half-lives of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were (0.75±0.22) and (0.86±0.19) min, and the clearance half-lives were (24.74±3.77) and (29.53±3.42) min. Biodistribution of normal mice showed that the uptake values in the liver, lungs, and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177Lu-PSMA-I&T ( t values: 4.24-8.36, all P<0.05). The tumor uptake of 177Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177Lu-PSMA-I&T ((0.856±0.183) vs (0.579±0.126) percentage activity of injection dose per gram of tissue (%ID/g); t=2.78, P=0.024) in 22Rv1 tumor-bearing mice. The rapid clearance pattern resulted in a higher tumor/muscle (T/M) ratio for 177Lu-PSMA-3Q (99.604±11.106), which was significantly higher than that for 177Lu-PSMA-I&T (45.078±10.444; t=7.80, P<0.001). According to SPECT imaging of patients with mCRPC, the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h, with significant difference ( t=7.62, P=0.002). Conclusion:177Lu-PSMA-3Q is easy to label, and has high yield and radiochemical purity, good stability, excellent biological performance, good targeting ability in patients, longer retention time, and fast background clearance rate, which is an ideal prostate cancer treatment drug targeting PSMA.

Objective:Exploring the clinical application effect of a series of digital designed guide plates in the repair of mandibular defects with free fibular muscle flap. Methods:A total of 32 patients who underwent fibular muscle flap repair of mandibular defects in the Head and Neck Tumor Surgery Department of Xi'an Jiaotong University Stomatological Hospital were selected as the research subjects. They were divided into a guide plate assisted group（16 cases） and a conventional surgery group（16 cases） according to the different surgical methods. The guide plate assisted group completed the surgery with the assistance of a digital design series of guide plates, while the conventional surgery group served as the control. Record the preparation and shaping time of two groups of fibular myocutaneous flaps, evaluate the surgical effect at least 6 months after surgery, and conduct a patient satisfaction survey. Use SPSS 16.0 software package to statistically process the data. Results:The preparation and shaping time of the fibular muscle flap in the guide plate assisted group were significantly shorter than those in the conventional surgery group（P<0.05）. The excellent and good rate（87.5%） of the guide plate assisted group in evaluating the surgical effect was significantly higher than that of the conventional surgery group（75.0%）（P<0.05）. The satisfaction scores of patients in the guide plate assisted group for facial shape and bite function recovery were significantly higher than those in the conventional surgery group（P<0.05）, while there was no significant statistical difference in the satisfaction scores of pronunciation function recovery between the two groups（P>0.05）. Conclusion:The design of digital guide plates can improve the accuracy of repairing mandibular defects with fibular flaps, shorten the preparation and shaping time of fibular flaps, restore good facial appearance and bite relationship of patients, and improve satisfaction. It is worth promoting and applying in clinical practice, but the design accuracy still needs to be continuously improved.
Humans ; Myocutaneous Flap ; Mandible/surgery* ; Fibula/transplantation* ; Plastic Surgery Procedures/methods* ; Male ; Free Tissue Flaps ; Female ; Middle Aged ; Mandibular Reconstruction/methods* ; Adult ; Patient Satisfaction

Objective To investigate the clinical efficacy of bone filling mesh bag combined with pedicle anchoring for the treatment of Stage Ⅲ reducible Kummell disease.Method The 35 paients with Stage Ⅲ reducible Kummell disease were treated with bone filling mesh bag combined with pedicle anchoring from January 2018 to December 2022.The operation Time,intraoperative blood lose,bone cement injection volume and surgical complications were recorded.The VAS score,ODI value,kyphosis Cobb angle and midline height of the injured vertebral were compared at preoperative,postoperative 1 day and last follow-up.Results All patients were followed up for 12-24 months[(15±3.5)months].Operation time was 35-63 min[(45±5.8)min],intraoperative blood loss was 10-35 ml[(20±5)ml],bone cement injection volume was 4.5-7.8 ml[(5.5±1.8)ml].There were 4 cases of bone cement leakage,there were 1 case of intervertebral leakage,2 cases of lateral leakage,1 case of anterior leakage and no patient with intracanal leakage.All bone cement leakage did not lead to clinical symptoms,bone cement poisoning and pulmonary embolism.No cement mass slip.All patients were followed up for 12 to 24 months[(15±3.5)months].VAS scores and Oswestry Disability Index(ODI)values were significantly lower on the first day after surgery than before surgery,with statistical significance(P＜0.05).The 3-month follow-up was slightly higher than that on the first day after surgery,and the difference was not statistically significant(P＞0.05).The midline height and Cobb Angle of the injured vertebra were measured by imaging.The height of the injured vertebra recovered significantly on the first day after operation,and the Cobb Angle decreased significantly,the difference was statistically significant(P＜0.05).The midline height of the injured vertebrae decreased and the Cobb Angle increased slightly at 3 months after the operation,but the difference was not statistically significant(P＞0.05).Conclusion In the the treatment of Stage Ⅲ reducible Kummell disease,Bone filling mesh bag combined with Pedicle anchoring have good clinical efficacy,which can significantly reduce the pain of patients,relieve clinical symptoms,improve spinal function,improve quality of life,and reduce the incidence of bone cement leakage and slippage.

Objective:To compare the clinical utility of 18F-prostate specific membrane antigen (PSMA)-1007 and 18F-FDG PET/CT imaging in newly diagnosed hepatocellular carcinoma (HCC). Methods:From April 2022 to July 2022, 17 patients (14 males, 3 females, age 36-73(54.4±10.1) years) with newly diagnosed HCC who underwent 18F-FDG and 18F-PSMA-1007 PET/CT imaging within 3 d in the First Affiliated Hospital of Zhengzhou University were prospectively enrolled. ROIs were drawn from normal liver tissue (L), abdominal aorta (A), right gluteus medius (M), and SUV max of these regions were compared with the SUV max of primary tumor (T). Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to analyze the data. Results:18F-FDG PT/CT, 18F-PSMA-1007 PET/CT and enhanced MRI detected 1(0, 2), 2(1, 5) and 2(1, 4) tumor lesions of the liver in each patient respectively ( H=7.10, P=0.029), and 18F-PSMA-1007 detected more lesions than 18F-FDG ( P=0.024). Although SUV max of 18F-PSMA-1007 in HCC was significantly higher than that of 18F-FDG (25.7(17.1, 45.1) vs 6.3(2.9, 12.4); z=3.39, P=0.001), there was no significant difference of T/L ratio between 18F-PSMA-1007 and 18F-FDG PET/CT imaging (2.7(2.1, 4.7) vs 1.6(1.0, 4.5); z=0.52, P=0.602). T/A and T/M ratios were significantly higher in 18F-PSMA-1007 PET/CT imaging than those in 18F-FDG PET/CT imaging ( z values: 3.15, 3.53, P values: 0.002, <0.001). 18F-PSMA-1007 PET/CT imaging found high uptake foci in the liver and ribs in 2 cases, which were pathologically confirmed as bone metastasis of HCC, while those lesions were not found by 18F-FDG imaging. Conclusion:Compared with 18F-FDG, 18F-PSMA-1007 PET/CT demonstrates higher tumor uptake, more intrahepatic tumors foci and distant bone metastases.

Objective:To explore the medical costs and influencing factors of patients diagnosed with Brucellosis in Datong of Shanxi province.Methods:Information on demographics, medical visits, and costs of patients diagnosed with Brucellosis between January 1, 2017, and December 31, 2019, were collected. Health care utilization and medical costs were analyzed from different genders, age groups, underlying diseases, clinical stages, and comorbidities.Results:A total of 2 289 patients (1 715 outpatient and 574 inpatient cases) were included in the analysis. 72.0% (1 649/2 289) were male, with an average age of (49.6±15.5) years; age between 45-59 years was the dominant group (36.2%,829/2 289). The mean age of inpatients (51.4±16.0) was higher than that of outpatients (49.0±15.2)( Z=-4.01, P<0.001). The average number of outpatient visits per outpatient was (1.6±1.5) times. The duration of hospitalization was (14.6±9.9) and (20.8±11.4) days for patients with central nervous system complications and (16.6±9.5) days for vascular system complications. Of the inpatients, 51.0% (293/574) had underlying diseases, and 30.3% (174/574) had endocrine and metabolic diseases. 54.0% (310/574) of inpatients were diagnosed with acute Brucellosis, and 46.0% (264/574) were diagnosed with chronic Brucellosis. A total of 64.3% (369/574) of inpatients had complications, 30.3% (174/574) of digestive system complications, followed by skeletal system complications (29.1%, 167/574). Among outpatients, age significantly affected medical costs ( P<0.001). For inpatients, age and complications and treatment effect were influential factors ( P<0.05). Patients with the combined skeletal system and central nervous system complications had significantly higher medical costs ( P<0.001). Conclusions:The medical costs for outpatient cases of Brucellosis were moderate. However, the economic burden was higher for inpatients, especially those with skeletal and neurological complications. Early detection, diagnosis, and treatment of cases were essential to avoid chronic Brucellosis and its complications and reduce medical costs.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.
Animals ; Bone Regeneration ; Indoles ; Nanoparticles ; Osteogenesis ; Pharmaceutical Preparations ; Polymers ; Rats