ObjectiveTo evaluate the relationship of human papillomavirus(HPV) intection with expressions of cell cycle regulatory proteins cyclin D1,E and their dependent kinase inhibitor p27 in bowenoid papulosis(BP).MethodsTissue specimens were obtained from the lesions of 44 patients with BP,and circumcised foreskin tissue from 10 males served as the control.Gene chip was used to determine the genotypes of HPV,and immunohistochemistry to quantify the expressions of cyclin D1,E,p27,in these specimens.Results Of the 44 BP specimens,all were positive for HPV DNA,38(86.36％) for high risk types of HPV,and 6 for low risk types of HPV.Of the high risk HPV-positive specimens,30(68.18％) harbored HPV16,16 harbored single HPV 16,14 harbored other types of HPV besides HPV 16,8 harbored other high risk types of HPV.HPV 6 predominated in low risk HPV-positive specimens.The expression of cyclin D1 was significantly higher in patients with high-risk HPV(u =53.00,P＜ 0.05),with both high and low risk HPV(u =5.00,P＜ 0.01) and with low risk HPV (u =22.50,P＜ 0.05) than in normal human controls,and higher in patients with both high and low risk HPV (u =44.00,P＜ 0.01) and with low risk HPV (u =22.50,P＜ 0.05) than those with high risk HPV.In the case of cyclin E expression,patients with high risk HPV (u =0.00,P ＜ 0.01 ),with both high and low risk HPV (u =4.00,P ＜ 0.01 ),and with low risk HPV(u =1.50,P ＜ 0.01 ) were higher than normal human controls,and patients with high risk HPV were higher than those with low risk HPV(u =11.00,P ＜ 0.01).No significant difference was observed in the expression of p27 between patients with high and low risk types of HPV.A significant increase was observed in the expression of p27 in patients aged ＞ 50 years compared with patients aged 20-30 years(u =47.00,P＜ 0.05) and aged 31-50 years (u =55.50,P＜ 0.05),as well as in the expression of cyclin E in patients aged ＞ 50 years compared with those aged 20-30 years(u =45.50,P ＜ 0.05),and in female patients compared with male patients (u =137.50,P＜ 0.05).ConlusionThere is a significant difference in the expression of cyclin D1,E and p27 among patients with BP infected with different types of HPV.

Objective:To investigate the clinical feature, diagnosis and treatment of autoimmune pancreatitis(AIP).Methods:Clinical data of 20 AIP patients admitted to the First Affiliated Hospital of University of Science and Technology of China from Jan 2014 to Dec 2019 were retrospectively analyzed.Results:Nineteen patients were diagnosed with type 1 AIP and 1 patient was with type 2 AIP. Fifteen patients were diagnosed by imaging, serology and other organ involvement, and 5 patients were confirmed by postoperative histopathology. Thirteen patients received glucocorticoid therapy. Five patients have not received glucocorticoid therapy after surgery.One patient refused treatment, and 1 patient is currently under clinical observation. Seventeen of the 20 patients were followed up, 11 patients were on glucocorticoid therapy with related clinical symptoms being gradually improved, serum IgG4 decreased and imaging findings improved. Five patients did not relapse after drug withdrawal. Three patients had recurrence of jaundice after drug withdrawal. One patient had recurrence of pancreatic lesions after drug withdrawal. Two patients had recurrence of high serum IgG4 after tapering the doses, these 6 patients were treated with steroid maintenance therapy. One patient died of repeated gastrointestinal bleeding 2 months later, and another 4 surgical patients and 1 patient under clinical observation are in good condition.Conclusions:AIP should be diagnosed in combination with clinical manifestations, serological examination, imaging examination and histopathology, especially focal lesions should be differentiated from pancreatic cancer, so as to avoid missed diagnosis and unnecessary surgical intervention.

Objective To evaluate the relationship between single nucleotide polymorphism(SNP) of candidate genes and radiation-induced esophagitis (RIE) in patients with lung cancer. Methods Between Jan. 2004 and Aug. 2006,170 patients with pathologically diagnosed lung cancer were enrolled in this study. The total target dose was 45-70 Gy( median 60 Gy). One hundred and thirty-two patients were treated with three-dimensional conformal radiotherapy(3DCRT) and 38 with two-dimensional radiotherapy(2DRT).Forty-one patients received radiotherapy alone, 78 received sequential chemoradiotherapy and 51 received concurrent chemoradiotherapy. Thirty-seven SNPs in 20 DNA repair genes were analyzed by using PCR-based restrieted fragment length polymorphism(RFLP). These genes were apoptosis and inflammatory cytoking genes including ATM, ERCC1, XRCC3, XRCC1, XPD, XPC, XPG, NBS1, STK15, ZNF350, ADPRT,TP53, FAS, FASL, CYP2D6 * 4, CASPASE8, COX2,TGF-β, CD14 and ACE. The endpoint was grade ≥2 R I E. Results Forty of the 170 patients developed grade ≥2 R I E, including 36 in grade 2 and 4 in grade 3. Univariate analysis revealed that radiation technique and concurrent chemoradiotherapy were statistically significant relatives to the incidence of R I E (P = 0. 032,0.049) , and both of them had the trend associating with the esophagitis( P = 0.072,0. 094 ). An increased incidence of esophagitis was observed associating with the TGF-β1-509T and XPD 751 Lys/Lys genotypes ( χ2 = 5.65, P = 0.017 ;χ2 = 3.84, P = 0. 048 )in multivariate analysis. Conclusions Genetic polymorphisms in TGF-β1 gene and XPD gene have a significant association with radiation-induced esophagitis.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

BACKGROUNDThe lung and esophagus are always damaged during radiation on thoracic tumors to a certain extent. This study is to report the incidence of radiation pneumonitis and radiation esophagitis and to analyze the factors as predictors of radiation toxicity in the treatment of three-dimensional conformal radiotherapy (3DCRT) for lung cancer.

METHODSBetween March 1999 and September 2003, 112 lung cancer patients treated with 3DCRT were reviewed at this Hospital. This population consisted of 87 men and 25 women, including 97 cases of non-small cell lung cancer and 15 of small cell lung cancer. The median age was 64 years old. Radiotherapy was delivered at 2Gy fraction, 5 fractions per week. The median total dose was 60Gy.

RESULTSGrade 2 or more acute radiation pneumonitis developed in 7.1% (8/112) of patients while grade 2 or more late radiation pneumonitis appeared in 1.8% (2/112) of patients. Acute radiation esophagitis was observed in 8.9% (10/112) of patients with grade 2. No clinical and physical factor was relative to acute radiation pneumonitis by univariate and multivariate analysis. In the entire population, the univariate analysis revealed that many parameters (pre-treatment weight loss more than 5%, chemotherapy and concurrent chemotherapy) were significantly associated with acute radiation esophagitis. Multivariate analysis revealed that pre-treatment weight loss more than 5% was the most important risk factor for acute radiation esophagitis (P= 0.016).

CONCLUSIONSNo clinical and physical factor is relative to acute radiation pneumonitis and pre-treatment weight loss more than 5% is the most important risk factor for acute radiation esophagitis in this study.

Objective:To analyze the failure mode after immunotherapy and the prognostic significance of combined radiotherapy for advanced non-small cell lung cancer (NSCLC).Methods:Clinical data of 220 advanced NSCLC patients receiving immune checkpoint inhibitors (ICI) as the first-line therapy in Tianjin Medical University Cancer Institute and Hospital from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, the first-line treatment regimen, modes and locations of failure, radiotherapy purpose, location and prescription dose of all patients were collected. The main parameter was the overall survival (OS). Survival analysis was conducted by Kaplan-Meier method. Survival comparison was performed by log-rank test.Results:A total of 220 patients were enrolled in the study in which 65 cases (29.5%) exhibited a state of oligometastasis. Among 72 patients who received radiotherapy, 29 cases (40%) received chest radiotherapy and 53 cases (74%) received metastatic radiotherapy. The median follow-up time was 25.6 months. Up to the last follow-up, disease progression had been observed in 140 patients, with 84 patients (38.2%) of them demonstrating a state of oligometastasis. Among 120 patients with disease progression and confirmed location of progression, 62 patients (51.7%) failed in first-line immunotherapy because of the primary lesion progression (mainly in the chest cavity), 34 patients (28.3%) due to the appearance of new metastases, and the remaining 24 patients(20.0%) due to primary lesion progression and new distant metastases. Among 72 patients treated with the first-line immunotherapy combined with local radiotherapy, 17 patients (24%) received planned radiotherapy, another 17 patients (24%) received salvage radiotherapy, and the remaining 38 patients (53%) received radiotherapy to relieve symptoms. The prognosis of patients significantly differed according to the purpose of radiotherapy ( P=0.030). The median OS of patients who did not receive radiotherapy was 29.1 months, those who received planned radiotherapy did not reach the median OS, and the median OS of those who received salvage radiotherapy was 28.7 months, and the median OS of those who received local radiotherapy to relieve symptoms was only 19.0 months. Conclusions:The progression of primary lesions is the main failure mode of the first-line immunotherapy. Chest cavity is the main location of tumor progression. Local radiotherapy for intrathoracic lesions may improve the survival benefit further for advanced NSCLC patients after the first-line immunotherapy.

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.