Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.

Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)％,(26.91±2.94)％,(19.28±1.52)％and(6.33±2.30)％;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P＜0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

Objective To explore the mechanism of inhibition of colorectal cancer cells HT29 proliferation,migration and invasion by bufalin through Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Human colorectal cancer HT29 cells were randomly divided into control group and experimental-L,-M,-H groups.The cells in the control group were not treated,and the cells in the experimental-L,-M,-H groups were treated with 2.5,5.0 and 10.0 μmol·L-1 bufalin for 48 h.After HT29 cells were infected with FLAG STAT3 lentivirus,the cells were divided into lentivirus infection group and experiment-H(10.0 pmol·L-1 bufalin)+lentivirus infection group.Cell viability was detected by cell counting kit 8(CCK-8).Cloning experiment to verify cell proliferation rate;Transwell experiment verified the migration ability of cells after bufalin treatment;the transfection efficiency of lentivirus and the expression of cell-related proteins were detected by Western blot.Results After 48 h of drug action,the number of cells in the control group,experimental-L,-M,-H groups were 1 003.25±255.53,698.00±152.25,562.13±31.56 and 449.50±82.40,respectively;the number of invasive cells were 932.00±188.84,742.22±108.64,514.67±124.82 and 343.56±86.42,respectively;the protein expression level of p-JAK2 were 1.37±0.27,0.97±0.06,0.74±0.06 and 0.39±0.12,respectively.The number of cells in the control group,experimental-H group,lentivirus infection group,and experimental-H+lentivirus infection group were 906.88±211.71,389.00±143.08,1 279.38±210.34 and 604.75±12.52,respectively;the number of invasive cells were 671.22±44.74,246.11±28.16,1 080.78±119.13 and 574.78±16.23,respectively.Compared with the control group,there were statistically significant differences in the number of cell proliferation,the number of cell invasion and the relative levels of p-JAK2 in the experimental-M and-H groups(all P＜0.05).Compared with the control group,the number of cell proliferation and the number of cell invasion in the experimental-H group,the lentivirus infection group,and the high-dose experimental+lentivirus infection group were statistically significant(all P＜0.05).Conclusion Bufalin can inhibit the proliferation,migration and invasion of colorectal cancer by activating the JAK2/STAT3 signalling pathway.

Objective:To explore the prospective associations between physical activity and incident ischemic stroke in adults.Methods:Data of China Kadoorie Biobank study in Tongxiang of Zhejiang were used. After excluding participants with cancers, strokes, heart diseases and diabetes at baseline study, a total of 53 916 participants aged 30-79 years were included in the final analysis. The participants were divided into 5 groups according to the quintiles of their physical activity level. Cox proportional hazard regression models was used to calculate the hazard ratios ( HR) for the analysis on the association between baseline physical activity level and risk for ischemic stroke. Results:The total physical activity level in the participants was (30.63±15.25) metabolic equivalent (MET)-h/d, and it was higher in men [(31.04±15.48) MET-h/d] than that in women [(30.33±15.07) MET-h/d] ( P<0.001). In 595 526 person-years of the follow-up (average 11.4 years), a total of 1 138 men and 1 082 women were newly diagnosed with ischemic stroke. Compared to participants with the lowest physical activity level (<16.17 MET-h/d), after adjusting for socio-demographic factors, lifestyle, BMI, waist circumference, and SBP, the HRs for the risk for ischemic stroke in those with moderate low physical activity level (16.17-24.94 MET-h/d), moderate physical activity level (24.95-35.63 MET-h/d), moderate high physical activity level (35.64-43.86 MET-h/d) and the highest physical activity level (≥43.87 MET-h/d) were 0.93 (95% CI: 0.83-1.04), 0.87 (95% CI: 0.76-0.98), 0.82 (95% CI: 0.71-0.95) and 0.76 (95% CI: 0.64-0.89), respectively. Conclusion:Improving physical activity level has an effect on reducing the risk for ischemic stroke.

Objective To detect the expression level of 4-aminobutyrate aminotransferase(ABAT)in bone marrow of patients with myelodysplastic syndrome(MDS),and analyze its influence on clinicopathological features and prognosis of patients.Methods From January 2016 to March 2020,92 patients with MDS and 30 patients with acute myeloid leukemia(AML)from the First Affiliated Hospital of Xingtai Medical College were retrospectively collected.Meanwhile,30 patients with immunothrombocytopenia who did not develop MDS or other clonal diseases of the blood system during a 3-year follow-up were collected as control group.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the relative expression level and methylation level of ABAT mRNA of all patients,and the relative expression level and methylation level of ABAT mRNA among different clinical characteristics of MDS patients were compared.Multivariate logistic regression analysis was used to analyze the risk factors affecting the adverse prognosis of MDS.The clinical value of detecting ABAT methylation level in predicting poor prognosis of MDS patients was analyzed by receiver operating characteristic(ROC)curve.Kaplan-Meier method was used to calculate the 3-year survival rate between groups with different ABAT mRNA relative expression levels and methylation levels,and log-rank test was used for their comparison.Results The expression level of ABAT mRNA in MDS group(0.42±0.08)was lower than that in control group(0.56±0.15)and AML group(0.52±0.10),while the methylation level of ABAT(32.51±5.32)was higher than that of AML group(26.21±4.58)and control group(10.25±4.31),and the differences were significant(t=4.251,4.562;10.415,8.326,all P<0.001).The methylation level of ABAT in high-risk patients(42.65±5.32)was higher than that in low-risk patients(25.63±4.16),intermediate-risk-1 patients(30.59±2.51)and intermediate-risk-2 patients(33.25±3.69)by IPSS risk grade,and the differences were significant(t=8.329,7.077,15.874,all P<0.001).Poor Karyotype analysis result[OR(95%CI):4.973(1.524～8.581),P=0.004],high IPSS risk grade[OR(95%CI):8.542(2.365～14.521),P<0.001]and ABAT hypermethylation level[OR(95%CI):6.178(1.589～13.021),P<0.001]were the risk factors affecting the poor prognosis of MDS.The cut-offvalue of ABAT methylation level to predict the poor prognosis of MDS were 30.54,and the area under the curve(AUC),the sensitivity and specificity were 0.92,0.874 and 0.851,respectively.The 3-year survival rate of the high ABAT methylation group(>30.54)was 66.67%,which was lower than that of the low ABAT methylation group(≤30.54)was 93.18%,with significant difference(Log-rank x2=9.814,P=0.002).Conclusion The ABAT methylation levels in MDS bone marrow increase,which is a risk factor affecting the poor prognosis of patients.ABAT basal level>30.54 is expected to become a factors predicting the poor prognosis of patients.

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.
Female ; Humans ; Vagina/microbiology* ; Uterine Cervical Neoplasms/genetics* ; Uterine Cervical Dysplasia ; Cervix Uteri ; Lactobacillus/genetics* ; Papillomavirus Infections

Objective:To investigate the influence of muscle energy technology (MET) combined with Maitland joint mobilization surgery on the elbow joint flexion function in patients with deep burn of elbow joint.Methods:A retrospective controlled clinical trial was conducted. From January 2020 to January 2022, 53 patients with elbow joint flexion dysfunction after deep burns who met the inclusion criteria were treated in Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 32 males and 21 females, aged (37±12) years. According to the treatment method used, the patients were divided into conventional treatment alone group (15 cases), conventional treatment+joint mobilization surgery group (18 cases), and conventional treatment+joint mobilization surgery+MET group (20 cases). Before treatment and 2 months after treatment, the patient's elbow joint range of motion was measured using a protractor, the Mayo elbow joint function score was used to evaluate elbow joint function, a portable muscle strength tester was used to measure elbow extensor muscle strength, and visual analogue scale was used to evaluate pain degree. Data were statistically analyzed with one-way analysis of variance, least significant difference test, paired sample t test, Kruskal-Wallis H test, Wilcoxon signed rank-sum test, chi-square test, Fisher's exact probability test, and Bonferroni correction. Results:After two months of treatment, the elbow joint range of motion and elbow joint function scores of patients in conventional treatment+joint mobilization surgery group and conventional treatment+joint mobilization surgery+MET group ((103±12)° and 60 (50, 66), (131±14)° and 73 (65, 80)) were significantly larger and higher than those in conventional treatment alone group ((77±15)° and 45 (35, 50), P values all <0.05), respectively. The elbow joint range of motion and elbow joint function scores of patients in conventional treatment+joint mobilization surgery+MET group were significantly larger and higher than those in conventional treatment+joint mobilization surgery group ( P values all <0.05), respectively. After two months of treatment, the elbow extensor muscle strength and pain score of patients in conventional treatment+joint mobilization surgery+MET group were respectively significantly larger and lower than those in conventional treatment alone group and conventional treatment+joint mobilization surgery group ( P values all <0.05). The elbow extensor muscle strength and pain score of patients in conventional treatment+joint mobilization surgery group were similar to those in conventional treatment alone group ( P>0.05). The elbow joint range of motion and elbow extensor muscle strength (with t values of 9.37, 25.54, 28.71, 6.70, 7.20, and 7.01, respectively, P<0.05), elbow joint function scores and pain scores (with Z values of 3.15, 3.63, 3.93, 3.30, 3.52, and 3.84, respectively, P<0.05) of patients in conventional treatment alone group, conventional treatment+joint mobilization surgery group, and conventional treatment+joint mobilization surgery+MET group after two months of treatment were significantly improved compared with those before treatment. Conclusions:The combination of MET and Maitland joint mobilization surgery can effectively improve elbow joint range of motion, elbow joint function, elbow extensor muscle strength, and pain of patients with deep elbow joint burns, therefore it is worthy of promotion.

Objective:To investigate the clinical application value of left ventricular myocardial strain obtained by cardiac MR (CMR) in recent major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods:From January 2020 to December 2020, a total of 163 patients successfully underwent primary PCI and underwent CMR examination within one week after surgery at Affiliated Hospital of Xuzhou Medical University. The scan sequences included rapid balance-fast field echo and late-gadolinium enhancement. CVI42 post-processing software was used to analyze and measure the left ventricular myocardial strain indices, including left ventricular global longitudinal strain (GLS), left ventricular global circumferential strain (GCS), and left ventricular global radial strain (GRS). According to the results of the 1-year follow-up after surgery, the patients were divided into the MACE group ( n=28) and the non-MACE group ( n=135). For continuous variables with a normal distribution, the t test of two independent samples was used for comparisons between groups. For continuous variables with an abnormal distribution, the variables were compared and analyzed by the rank sum test. For categorical variables, the χ 2 tests were used for between-group comparisons. Cox regression was used to analyze the prognostic value of myocardial strain on the development of MACE in patients with STEMI. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of myocardial strain parameters, and the optimal cut-off value was evaluated by calculating the Youden index. Results:The GLS, GCS, and GRS of the MACE group were (-10.4±3.3)%, [-11.9 (-14.5, -9.3)]%, and (18.3±6.3)%, respectively, and those of the non-MACE group were (-13.7±3.4)%, [-14.6 (-16.4, -11.7)]%, and (22.3±6.1)%, respectively. The difference between the two groups was statistically significant ( t/ Z=-4.71, -3.04, 3.21, P<0.05). Multivariate Cox regression analysis showed that GLS was an independent predictor of MACE (HR=1.546, 95%CI 1.180-2.027, P=0.002). The ROC curve analysis showed that GLS had the largest area under the curve (AUC) (AUC=0.754, 95%CI 0.658-0.851, P<0.001), with a cut-off value of -12.45%. Its diagnostic sensitivity was 71.4%, and the specificity was 67.4%. The value was better than that of the traditional predictor of STEMI prognosis, namely, left ventricular ejection fraction (AUC=0.680, 95%CI 0.567-0.793, P=0.003). Conclusion:GLS of CMR is an independent predictor of MACE in STEMI patients undergoing primary PCI.

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.