Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

Objective:To observe the effect of hyperthermia combined with iron overload on the regulation of tumor-associated macrophage polarization and the migration ability of CAL-27 cells and explore its mechanism.Methods:Human monocytic leukemia cell THP-1 was induced and polarized into M2 macrophages. M2 tumor-associated macrophages and CAL-27 cells were divided into the control group (no intervention), hyperthermia group (incubated at 42 ℃ for 1 h, and then incubated at 37 ℃ for 24 h), ferric citrate group (added with 2.5 mg/ml ferric citrate, and cultured in an incubator at 37 ℃for 24 h) and hyperthermia + ferric citrate group (added with 2.5 mg/ml ferric citrate for 1 h, cultured in an incubator at 42℃ for 1 h, and then incubated at 37℃ for 24 h). For M2 macrophage groups, the mRNA relative expression levels of surface markers of M1 macrophage polarization including interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and those of M2 macrophage polarization including IL-10 and transforming growth factor-β(TGF-β) were detected by real-time reverse transcription polymerase chain reaction. The expression levels of IL-1β and IL-10 were detected by ELISA. The expression levels of CD86 (surface marker of M1 macrophage polarization) and CD206 (surface marker of M2 macrophage polarization) were measured by flow cytometry. The expression levels of signal transducer and activator of transcription 3 (STAT3), Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) and phosphorylated (p)-NF-κB were detected by Western blot (WB). The migration ability of CAL-27 cells was assessed by scratch assay.Results:Compared with the control group, the expression levels of IL-1βand TNF-α mRNA, and IL-1βand CD86 proteins were up-regulated, whereas those of IL-10 and TGF-β mRNA, and IL-10 and CD206 proteins were down-regulated in the hyperthermia, ferric citrate and hyperthermia + ferric citrate groups, respectively (all P<0.05). In addition, the changes in the hyperthermia+ferric citrate group were significantly larger than those in the hyperthermia and ferric citrate groups (all P<0.05). WB showed that the expression level of STAT3 protein was down-regulated and those of TLR4, NF-κB and p-NF-κB expression were up-regulated in the hyperthermia + ferric citrate group (all P<0.05). Scratch assay showed that the migration ability of CAL-27 cells was inhibited in the hyperthermia, ferric citrate and hyperthermia + ferric citrate groups ( P<0.001), and the changes in the hyperthermia + ferric citrate group were significantly more pronounced than those in the hyperthermia and ferric citrate groups (both P<0.001). Conclusions:Hyperthermia and iron overload can promote the polarization of M1 macrophages and inhibit the polarization of M1 macrophages into M2 macrophages, thereby suppressing the migration of oral squamous cell carcinoma. The mechanism may be related to inhibiting the expression of STAT3 and activating the TLR4/NF-κB signaling pathway.

Objective:To excplore the risk factors for myocardial damage in patients with systemic lupus erythematosus (SLE) and the value of application of resting gated nuclear myocardial imaging.Methods:A total of 64 lupus patients who were hospitalized in Wuxi People′s Hospital from January 2021 to December 2022 were included, and the patients′ clinical data, imaging data, and test reports were retrospectively analyzed using paired χ2 test, t test, Wilcoxon rank-sum test, Mann-Whitney U test, and binary logistic regression analysis. Results:①Among the 64 patients with lupus, 19(29.7%) had abnormal radionuclide myocardial imaging, 23 (35.9%) had elevated BNP, and 6 (9.4%) had myocardial involvement on echocardiography. There was no statistical difference between radionuclide myocardial imaging and BNP ( Kappa=0.294, P=0.503), but there was a significant difference between radionuclide myocardial imaging and echocardiography ( Kappa=0.394, P<0.001). ②There was no statistical difference in the EF values measured by resting gated myocardial radionuclide imaging and echocardiography [(64.9±9.6)% vs. (63.2±5.6)%, Z=-1.73, P=0.083]. ③Compared with the normal myocardial group, the myocardial damage group had higher BNP value [(912±1729)pg/ml vs. (297±572)pg/ml, t=-3.05, P=0.002], ESR[(56±42)mm/1 h vs. (34±27)mm/1 h, t=-2.17, P=0.030], and SDI scores[2.16±1.30 vs. 1.04±0.85, t=-3.43, P=0.002], more patients with a course of disease≥10 years [57.9% vs. 28.9%, Z=2.17, P=0.030], and anti-U1RNP antibody[52.6% 24.4%, Z=-2.18, P=0.029] and anti-SSB antibody[31.6% vs. 11.1% Z=-1.97, P=0.049] were statistically different. ④Through binary logistic regression analysis, SDI score [ OR ( 95%CI)=2.444 (1.195, 4.998), P=0.014], anti-U1RNP antibody [ OR ( 95%CI)=4.569 (1.036, 20.150), P=0.045] and disease duration≥10 years [ OR ( 95%CI)=5.218 (1.210, 22.496), P=0.027] were independent risk factors for myocardial damage in SLE patients. Conclusion:Resting gated radionuclide myocardial imaging can accurately provide ventricular motion parameters and can detect myocardial damage in SLE patients at early stage. Disease duration ≥10 years, high SDI score, and positive anti-U1RNP antibodies are independent risk factors for myocardial damage in SLE patients.

Objective:To excplore the risk factors for myocardial damage in patients with systemic lupus erythematosus (SLE) and the value of application of resting gated nuclear myocardial imaging.Methods:A total of 64 lupus patients who were hospitalized in Wuxi People′s Hospital from January 2021 to December 2022 were included, and the patients′ clinical data, imaging data, and test reports were retrospectively analyzed using paired χ2 test, t test, Wilcoxon rank-sum test, Mann-Whitney U test, and binary logistic regression analysis. Results:①Among the 64 patients with lupus, 19(29.7%) had abnormal radionuclide myocardial imaging, 23 (35.9%) had elevated BNP, and 6 (9.4%) had myocardial involvement on echocardiography. There was no statistical difference between radionuclide myocardial imaging and BNP ( Kappa=0.294, P=0.503), but there was a significant difference between radionuclide myocardial imaging and echocardiography ( Kappa=0.394, P<0.001). ②There was no statistical difference in the EF values measured by resting gated myocardial radionuclide imaging and echocardiography [(64.9±9.6)% vs. (63.2±5.6)%, Z=-1.73, P=0.083]. ③Compared with the normal myocardial group, the myocardial damage group had higher BNP value [(912±1729)pg/ml vs. (297±572)pg/ml, t=-3.05, P=0.002], ESR[(56±42)mm/1 h vs. (34±27)mm/1 h, t=-2.17, P=0.030], and SDI scores[2.16±1.30 vs. 1.04±0.85, t=-3.43, P=0.002], more patients with a course of disease≥10 years [57.9% vs. 28.9%, Z=2.17, P=0.030], and anti-U1RNP antibody[52.6% 24.4%, Z=-2.18, P=0.029] and anti-SSB antibody[31.6% vs. 11.1% Z=-1.97, P=0.049] were statistically different. ④Through binary logistic regression analysis, SDI score [ OR ( 95%CI)=2.444 (1.195, 4.998), P=0.014], anti-U1RNP antibody [ OR ( 95%CI)=4.569 (1.036, 20.150), P=0.045] and disease duration≥10 years [ OR ( 95%CI)=5.218 (1.210, 22.496), P=0.027] were independent risk factors for myocardial damage in SLE patients. Conclusion:Resting gated radionuclide myocardial imaging can accurately provide ventricular motion parameters and can detect myocardial damage in SLE patients at early stage. Disease duration ≥10 years, high SDI score, and positive anti-U1RNP antibodies are independent risk factors for myocardial damage in SLE patients.

Objective:To observe the effect of hyperthermia combined with iron overload on the regulation of tumor-associated macrophage polarization and the migration ability of CAL-27 cells and explore its mechanism.Methods:Human monocytic leukemia cell THP-1 was induced and polarized into M2 macrophages. M2 tumor-associated macrophages and CAL-27 cells were divided into the control group (no intervention), hyperthermia group (incubated at 42 ℃ for 1 h, and then incubated at 37 ℃ for 24 h), ferric citrate group (added with 2.5 mg/ml ferric citrate, and cultured in an incubator at 37 ℃for 24 h) and hyperthermia + ferric citrate group (added with 2.5 mg/ml ferric citrate for 1 h, cultured in an incubator at 42℃ for 1 h, and then incubated at 37℃ for 24 h). For M2 macrophage groups, the mRNA relative expression levels of surface markers of M1 macrophage polarization including interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and those of M2 macrophage polarization including IL-10 and transforming growth factor-β(TGF-β) were detected by real-time reverse transcription polymerase chain reaction. The expression levels of IL-1β and IL-10 were detected by ELISA. The expression levels of CD86 (surface marker of M1 macrophage polarization) and CD206 (surface marker of M2 macrophage polarization) were measured by flow cytometry. The expression levels of signal transducer and activator of transcription 3 (STAT3), Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) and phosphorylated (p)-NF-κB were detected by Western blot (WB). The migration ability of CAL-27 cells was assessed by scratch assay.Results:Compared with the control group, the expression levels of IL-1βand TNF-α mRNA, and IL-1βand CD86 proteins were up-regulated, whereas those of IL-10 and TGF-β mRNA, and IL-10 and CD206 proteins were down-regulated in the hyperthermia, ferric citrate and hyperthermia + ferric citrate groups, respectively (all P<0.05). In addition, the changes in the hyperthermia+ferric citrate group were significantly larger than those in the hyperthermia and ferric citrate groups (all P<0.05). WB showed that the expression level of STAT3 protein was down-regulated and those of TLR4, NF-κB and p-NF-κB expression were up-regulated in the hyperthermia + ferric citrate group (all P<0.05). Scratch assay showed that the migration ability of CAL-27 cells was inhibited in the hyperthermia, ferric citrate and hyperthermia + ferric citrate groups ( P<0.001), and the changes in the hyperthermia + ferric citrate group were significantly more pronounced than those in the hyperthermia and ferric citrate groups (both P<0.001). Conclusions:Hyperthermia and iron overload can promote the polarization of M1 macrophages and inhibit the polarization of M1 macrophages into M2 macrophages, thereby suppressing the migration of oral squamous cell carcinoma. The mechanism may be related to inhibiting the expression of STAT3 and activating the TLR4/NF-κB signaling pathway.

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.

Objective:To investigate the diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatica (PMR). Methods:From November 2014 to December 2022, 177 patients (119 males, 58 females; age: 67.0 ( 61.0, 72.0) years) admitted to the Department of Rheumatology and Immunology, the First People′s Hospital of Changzhou, with suspected PMR and undergoing 18F-FDG PET/CT examination were retrospectively analyzed. Patients were randomly divided into training set and validation set at the ratio of 7∶3. Three machine learning models, including classification and regression tree (CART), the least absolute shrinkage and selection operator (LASSO) algorithm, and logistic regression, were established based on the PET/CT imaging features to aid in the diagnosis of PMR. The diagnostic efficacy of each model was evaluated by ROC curve analysis and differences among AUCs were analyzed by Delong test. Results:There were 78(44.1%, 78/177) PMR patients and 99(55.9%, 99/177) non-PMR patients, and 124 patients in the training set and 53 patients in the validation set. The logistic regression model (training set: AUC=0.961; validation set: AUC=0.930) was superior to the CART (training set: AUC=0.902, z=2.96, P=0.003; validation set: AUC=0.844, z=2.46, P=0.014) in diagnosing PMR, and was similar to LASSO algorithm (training set: AUC=0.957, z=0.95, P=0.340; validation set: AUC=0.930, z=0.00, P=1.000), but with fewer sites evaluated. The simplified PMR-Logit score had the AUC of 0.951 in the overall population, with the sensitivity of 89.74%(70/78) and the specificity of 90.91%(90/99). Conclusion:Machine learning models based on 18F-FDG PET/CT imaging features are expected to be an effective diagnostic tool for PMR.

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Objective To investigate the effects and mechnism of abnormal stress promoting macrophage mobility inhibitory factor(MIF),cyclooxygenase 2(COX2)and prostaglandin E2(PGE2)in the progression of temporomandibular joint osteoarthritis(TMJOA).Methods From January 2020 to December 2021,TMJOA and temporomandibular joint internal derangement(TMJID)patients(30 cases in each group,we divided the TMJOA into group TMJ Ⅰ,Ⅱ,Ⅲ according to the stage)who were admitted to TMJOA special clinic of the First Affiliated Hospital of Xinjiang Medical University and accompanied by abnormal occlusion were collected.The pain score of the occlusal state of the patients was evaluated by visual analogue scale.The expression levels of MIF,COX2 and PGE2 in synovial fluid were detected by ELISA.We used the unilateral anterior crossbite for TMJOA(UAC)rats model(the grouped into:UAC-4 weeks,UAC-8 weeks and UAC-12 weeks group),and control group at the same time(grouped into:Ctrl-4 weeks,Ctrl-8 weeks and Ctrl-12 weeks group),each group had 6 rats.The expression levels of MIF,COX2 and PGE2 in serum and synovial fluid of rats were detected by ELISA.The expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2 in temporomandibular joint of rats were detected by Western blotting.The fluid flow shear stress(FFSS)model of fibroblast-like synovial cells(FLSs)was established,and the mRNA and protein expression levels of above indexes were detected by RT-PCR and Western blotting.Results Visual analogue scale evaluation showed that the pain score of TMJOA Ⅰ and Ⅱ group was significantly higher than that of TMJID(P<0.001).ELISA results showed that the expression levels of MIF,COX2 and PGE2 in synovial fluid in TMJOA group were higher than those in TMJID group(P<0.05),and the expression levels were the highest in TMJOA Ⅱ group.Compared with control group,the expressions of MIF,COX2 and PGE2 in serum and synovial fluid at UAC-4 weeks,8 weeks and 12 weeks were slightly higher,and significantly higher at UAC-8 weeks in rat TMJOA model(P<0.05).In addition,the expression trend of protein levels in temporomandibular joint tissues was similar,which showed higher expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2(P<0.05).In the cell model where FFSS interfered with FLSs,with the increase of FFSS,cell with deformation,incomplete cell membrane and reduced number.Compared with control group,the expression levels of IL-1β,IL-18,MIF,COX2 and PGE2(PTGER2)of FLSs were increased in 1,3,5 and 10 dyn/cm2 intervention groups(P<0.05).Conclusion MIF,COX2 and PGE2 were highly expressed in temporomandibular joint synovial fluid of TMJOA patients with malocclusion.And these three factors were also highly expressed in serum and synovial fluid of UAC rats.The abnormal fluid shear stress promotes the secretion of MIF,COX2 and PGE2 by FLSs to participate in joint microenvironment inflammation and accelerate disease progression.