Objective:To investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis.Methods:A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer.Results:HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients ( P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions:HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.

Objective:To investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis.Methods:A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer.Results:HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients ( P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions:HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.

Objective: MRI images were used to study the efficacy of anterior repositioning splint (ARS) in the treatment of different types of disc displacement with reduction (DDWR) in temporomandibular joint. Methods: From September 2020 to December 2021, 26 patients with DDWR were enrolled in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 21 females with an average age of (20.8±5.8) years. ARS was used for 3-6 months. The changes of joint clicking, opening type and joint pain before and after treatment were compared. The changes of disc position, disc-condyle angle and condylar bone mass before and after treatment were compared by MRI. Paired t-test was performed on the disc-condyle angle before and after treatment, Fisher's exact test was performed on the change of disk position, and other count data were expressed as rate (%). Results: After ARS treatment, the effective rates of joint clicking,abnormal opening, joint pain and disc displacement were 97%(35/36), 14/18, 7/9 and 95%(36/38). MRI analysis found that there was a significant difference between the disc position before and after treatment (P<0.001), MRI analysis showed that the anterior disc displacement (48%, 25/52) and the anterolateral disc displacement (17%, 9/52) were the most common before treatment. In contrast, the normal superior disc (75%, 39/52) and the anterior disc displacement (17%, 9/52) were the most common after treatment, no significant changes were seen after treatment in the anteromedial disc displacement. The disc-condylar angle was (36.09±19.02) ° before ARS treatment and (3.94±10.12) ° after ARS treatment(t=9.23, P<0.001). After treatment, 46% (12/16) of the patients showed new bone formation, and the height of the condyle recovered. Conclusions: The clinical efficacy of ARS in the treatment of anterior disc displacement and anterolateral displacement of temporomandibular joint is remarkable, which can restore the disc-condylar relationship of most patients with indications.
Adolescent ; Adult ; Arthralgia ; Female ; Humans ; Joint Dislocations/therapy* ; Magnetic Resonance Imaging ; Male ; Splints ; Temporomandibular Joint ; Temporomandibular Joint Disc/diagnostic imaging* ; Young Adult

Objective To analyze and investigate the correlation between the CYP2C19 gene polymorphism and clopidogrel cura-tive effect in the patients with coronary heart disease (CHD) to provide valuable reference information for the future clinical work. Methods A total of 128 cases of CHD undergoing PCI in our hospital from January 2015 to January 2016 were selected as the re-search subjects.All of them were treated with clopidogrel ,the loading dose was 300mg ,and the maintenance dose was 75mg.The subjects were divided into the clopidogrel resistance group and response group.The drug-metabolizing CYP2C19 genotype was com-pared between the two groups and the effect of CYP2C19 genotype on the clopidogrel response was observed.Results Among the subjects ,27 cases were clopidogrel resistance.A total of 16 cases of CYP2C19 slow metabolic gene carriers were detected.There was statistically significant difference between the patients with chronic metabolic genotype VASP-PRI with fast metabolic geno-type and intermediate metabolic genotype(P<0.05).The incidence rate of adverse end point events had statistical difference be-tween the clopidogrel resistance group and clopidogrel response group(P<0.05).Conclusion In the risk factors of clopidogrel re-sistance ,slow metabolism CYP2C19 genotype and clopidogrel resistance will increase the risk of clinical adverse endpoint events oc-currence ,clinic should give adequate attention.