BACKGROUND:Successful uterine spiral artery remodeling is necessary for normal pregnancy,in which vascular smooth muscle cells are important cells.Interferon-γ is associated with the loss of vascular smooth muscle cells during early pregnancy.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the effects of interferon-γ on migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway. METHODS:Human vascular smooth muscle cells were divided into control group and interferon-γ group.The control group was cultured normally,and the interferon-γ group was treated with 10 ng/mL interferon-γ for 24 hours.The migration ability of vascular smooth muscle cells was detected by Transwell assay.The apoptosis of vascular smooth muscle cells was detected by TUNEL assay and flow cytometry.The mRNA expression levels of NLRP3 and caspase-1 were detected by qPCR.Western blot assay was utilized to detect NLRP3,caspase-1,and cleaved N-terminal GSDMD protein expression levels. RESULTS AND CONCLUSION:Compared with the control group,the migration ability and apoptosis rate of vascular smooth muscle cells in interferon-γ group were significantly increased(P<0.05).Compared with the control group,the mRNA expression levels of NLRP3 and caspase-1 in vascular smooth muscle cells of interferon-γ group were significantly increased(P<0.05).Compared with control group,the expression levels of NLRP3,caspase-1,and cleaved N-terminal GSDMD protein in vascular smooth muscle cells in the interferon-γ group were significantly increased(P<0.05).The results suggest that interferon-γ may regulate the migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

In recent years, the bacteriophage Φ29 (Phi29) DNA polymerase has garnered increasing attention due to its high-fidelity amplification capacity at constant temperatures. To advance the industrial application of this type of isothermal polymerases, this study mined and characterized new enzymes from the microbial metagenome based on the known Phi29 DNA polymerase sequence. The results revealed that a new enzyme, Php29 DNA polymerase, was identified in the microbial metagenome with plants as the hosts. This enzyme exhibited higher strand displacement activity, with a 59.5% similarity to bacteriophage Φ29. Experimental validation demonstrated that the enzyme had 3'→5' exonuclease activity, and its amplification products can serve as substrates for further catalytic reactions. The discovery and validation of Php29 DNA polymerase gives insights into the future industrial application of isothermal polymerases.
DNA-Directed DNA Polymerase/metabolism* ; Bacillus Phages/genetics* ; Metagenome

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.

Purpose To investigate the clinicopathologic,immunophenotypic features,genetic alterations and prognosis of melanotic Xp11 neoplasms/melanotic TFE3-rearrangement neo-plasms.Methods Five cases were selected from the Depart-ment of Pathology,Union Hospital,Huazhong University of Sci-ence and Technology from November 2018 to July 2023.The clinicopathologic,immunohistochemical,FISH assays,next-generation sequencing(NGS)and follow-up details were collect-ed.Results There were 1 male and 4 females,with their ages ranging from 16 to 59 years(mean 28.2 years).The maximum diameters of the masses were 3-6 cm(average 4.7 cm).The tumors located in right kidneys(3 cases),tubal interstitium(1 case)and pelvis(1 case).Microscopically,most tumors shared similar morphology such as nested,acinar structures sep-arated by a delicate vascular network.Epithelioid tumor cells presented with clear to granular eosinophilic cytoplasm.Lym-phocytic infiltration was seen in the background;melanin depo-sition was noted in the cases;neoplastic necrosis was detected in 4 cases.Mitotic activity was low with 5 cases showing＜3/10 HPF.Intravascular tumor thrombus was detected in 2 cases,no lymphovascular and nerve invasions were detected in other 3 ca-ses.Immunohistochemically,all 5 cases expressed TFE3 dif-fusely,and expressed HMB45,Melan A to varying degrees,CK(AE1/AE3),CK7,EMA,PAX8,TFEB,S-100,SOX10,SMA,desmin were all non-reactive in the 5 cases.The Ki67-la-beling index was＜20％.TFE3 separation signal in 4 cases were detected by FISH,1 case was interpreted as negative due to atypical signal which was confirmed by next-generation se-quencing(NGS)assay as RBM10-TFE3.Clinical follow-up was available for five patients for 2-60 months,in which four pa-tients were alive with no evidence of disease after initial resec-tion,and one patient with thoracic spine metastasis was currently in stable condition.Conclusion Melanotic Xp1 1 neoplasms/melanotic TFE3-rearrangement neoplasms has unique morpholog-ic,immunophenotypic and genetic characteristics.It might be reclassified into a distinctive malignant mesenchymal tumor enti-ty.

Objective To analyze the influencing factors of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy,and to explore the adverse effects of sarcopenia on patients with ad-vanced lung cancer undergoing anti-tumor therapy.Methods Patients with advanced lung cancer who received anti-tumor therapy in the Department of Oncology of a tertiary hospital in Chengdu from January to December 2021 were continuously included.The incidence situation of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy was evaluated by using the 12th thoracic spine (T12) skeletal muscle index (SMI) standard.According to the diagnostic criteria of sarcopenia,the patients were divided into the sarcope-nia group and the non-sarcopenia group.Multivariate logistic regression was used to analyze the influencing factors of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy.Results A total of 285 patients were included in this study,of which 123 cases (43.15％) were diagnosed as sarcopenia.Multiva-riate analysis showed that gender (P<0.001),pathological stage (P=0.012),creatinine (P=0.031) and BMI (P<0.001) were the influencing factors of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy.The quality of life score of patients in the sarcopenia group was significantly lower than that in the non-sarcopenia group (P=0.035).Conclusion The incidence of sarcopenia in patients with ad-vanced lung cancer undergoing anti-tumor therapy is high,which is related to many factors and affects the quality of life.

Objective:To investigate the clinical characteristics and treatment strategies of patients with connective tissue disease (CTD) related lymphatic duct obstruction.Methods:The clinical data, laboratory tests results, imaging data, and treatment of CTD patients associated with lymphatic vessel obstruction were retrospectively collected from January 2008 to December 2020 at Beijing Shijitan Hospital. Lymphatic duct obstruction was confirmed by thoracic duct ultrasound or thoracic duct MRI or lymphoscintigraphy or direct lymphangiography. SLE and RA patients were matched with gender and age in a 1∶2 ratio, and SLE and RA patients without lymphatic reflux disorder admitted at the same time were randomly selected as the control group. When comparing the data between the two groups, t-test or rank sum test was used to test continuous variables, and chi-square test or Fisher′s exact probability method was used to test categorical variables. Results:Forty-four patients with CTD complicated with thoracic duct obstruction were included, with a male-to-female ratio of 7∶37, including 14 cases of rheumatoid arthritis (RA), 21 cases of systemic lupus erythematosus (SLE), 8 cases of primary Sjogren's syndrome (pSS), and 1 case of systemic sclerosis (SSc). The onset age of CTD ranged from 14 to 68 years, the mean age was (37±15) years and the median duration of CTD was 66 (range 1~480) months. The median age at the onset of lymphatic duct obstruction such as limb edema or thoracoabdominal effusion was (42±17) years, and the median duration of lymphatic duct obstruction symptoms was 12 (range 3~480) months. 59%(26/44) of patients were diagnosed with CTD followed by the diagnosis of thoracic duct obstruction, and 41%(18/44) of patients had lymphatic duct obstruction symptoms as the initial presentation of CTD. Thoracic duct-related imaging was performed in 44 patients and showed thoracic duct obstruction (64%, 28/44), thoracic duct malformation or variation (36%, 16/44), limb lymphatic reflux disorder (34%, 15/44), and small bowel lymphatic duct dilatation or intestinal protein loss (18%, 8/44), respectively. Compared with the control group, among these patients, patients with RA complicated with lymphatic involvement had a younger onset age [(34±14)years old vs. (44±13)years old, t=-2.15, P=0.037)] and longer RA course [(17±11)months vs. (7±7)months, t=3.38, P=0.002] and presented with limb swelling (12/14). While compared with the control group, SLE patients complicated with lymphatic duct obstruction presented with celiac multi-plasmatic effusion (20/21), more patients presented with multiple serous cavity effusion [95%(20/21) vs. 62%(25/42), χ2=7.63, P=0.006], but the prevalence of lupus nephritis [(60%(12/21) vs. 86%(36/42), χ2=4.87, P=0.027] and lupus encephalopathy [0%(0/21) vs. 16.7%(17/42), χ2=6.11, P=0.013] was lower. 27% (12/44) of patients improved with aggressive glucocorticoids combined with immunosuppressive therapy, 54%(24/44) of patients were performed with lymphatic duct reconstruction surgery on top of medical treatment, 5 patients were lost of follow-up, and 2 patients deceased. Conclusion:CTD patients may develop lymphatic duct obstruction during the disease course, while lymphatic duct obstruction can also be the initial presentation of CTD. Rheumatologists and surgeons should be alert to this rare situation. Young women with refractory polyserositis or lymphedema should be examined for the possibility of combined CTD. Lymphatic duct obstruction may be associated with long-term chronic inflammation in CTD. Glucocorticoids combined with immunosuppressive agents and surgery can be used to treat lymphatic duct obstruction in patients with CTD.

Objective:To evaluate the safety and clinical efficacy of hypofractionated radiotherapy (HFRT) at 36.5 Gy in 10 fractions for the chest wall and reginal lymph nodes following modified radical mastectomy for breast cancer.Methods:This was a prospective, single-arm, phase Ⅱ clinical study. A total of 85 patients who received HFRT at 36.5 Gy in 10 fractions to the chest wall ± supraclavicular region following modified radical mastectomy for locally advanced breast cancer from March 2014 to December 2015 were included. The primary endpoint was radiotherapy toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS), and overall survival (OS).Results:The median follow-up period was 98 (94.0-109.0) months. Radiotherapy toxicities were mild. The incidence rates of grade 1 acute cutaneous and pulmonary toxicities were 52.9% and 40%, and those of grade 1 late cutaneous, pulmonary, and cardiac toxicities and upper extremity edema were 10.6%, 29.4%, 2.4%, and 21.2%, respectively. Only 1 (1.2%) patient suffered from grade 2 radiation-induced brachial plexus injury. Of the 85 patients, one patient had regional recurrence (supraclavicular lymph nodes), six patients had distant metastasis, and six patients died of breast cancer. The 9-year LRFFS, DFS, and OS were 97.7%, 91.8%, and 92.8%, respectively.Conclusions:HFRT at 36.5 Gy in 10 fractions following modified radical mastectomy for breast cancer is associated with mild toxicities. A phase Ⅲ study is necessary for validating HFRT's clinical efficacy.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.