1.HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression
Xiurong DU ; Muheng TAO ; Yongqin JIA ; Tingting WU ; Kaijian LING ; Yanzhou WANG ; Zhiqing LIANG
Journal of Army Medical University 2024;46(7):715-724
Objective To explore the effects of HPV16 E6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.Methods HUCEC models infected with HPV16 E6 were constructed,and transcriptome sequencing was performed to screen for differentially expressed genes(DEGs),which were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis,the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition,RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines,SiHa and CaSki.Results A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes;KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6,and RT-qPCR and Western blotting confirmed that HPV16 E6 down-regulated DHRS2 mRNA(P<0.01)and protein(P<0.05)and ETV5 protein expression(P<0.01).In SiHa and CaSki cells,compared with the control group,the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression(P<0.05).Conclusion HPV16 E6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating DHRS2 expression.
2.Safety and feasibility of day surgery management model under ERAS concept for gynecologic laparoscopic surgery
Huaying LIU ; Ling LI ; Yuanxiang SHI ; Xin RONG ; Xiaolong LIANG ; Yanzhou WANG ; Zhimin WU
Journal of Army Medical University 2024;46(14):1658-1665
Objective To explore the safety and feasibility of the application of day surgery management model under enhanced recovery after surgery(ERAS)concept in patients undergoing gynecologic laparoscopic surgery.Methods A non-randomized concurrent control trial was conducted on the patients who underwent laparoscopic surgery in our department from January to August 2021.A total of 92 patients admitted on odd date were assigned into Ward B of our department and served as the control group,and another 96 patients hospitalized on even date were subjected into Ward A and served as the observation group.The control group was given the routine treatment schedule,including the relevant examinations after admission and general operation procedure during hospitalization.The observation group was under a day surgery management model based on the concept of ERAS,with aid of a day surgery team and optimized perioperative management measures,including pre-hospital rehabilitation,shortening water fasting before surgery,multi-mode analgesia,preventive antiemesis,intraoperative warmth,prevention of deep vein thrombosis,immediate postoperative eating and activity,and follow-up after discharge.Postoperative subjective comfort,intestinal function recovery,social and economic benefits,postoperative complications and inflammatory indicators were compared between the 2 groups.Results In 0~6,7~12 and 13~24 h after operation,the scores of thirst,hunger,nausea,pain,abdominal distension and pharyngeal discomfort were significantly lower in the observation group than the control group(P<0.01).The observation group had obviously shorter length of hospital stay and ealier bowel sound recovery and first anal exhaust than the control group(P<0.01).No postoperative complication,such as fall,unplanned secondary operation or wound infection was observed in both groups.The postoperative inflammatory indicators,including procalcitonin(PCT),neutrophil percentage(Neu%)and white blood cell count(WBC)were all in the normal ranges in the 2 groups at 24 h and 3 and 7 d after surgery.Statistical differences were found in firstly postoperative mobilization,length of hospital stay,hospitalization cost and patient satisfaction between the 2 groups(P<0.01).Conclusion ERAS-based day surgery management model has the advantages of shortening hospital stay,reducing medical costs,promoting postoperative rehabilitation,and improving the comfort and satisfaction in patients undergoing gynecologic laparoscopic surgery.
3.Innovation of LESS-OPEN concept and its application and prospect in ovarian cystectomy
Journal of Army Medical University 2024;46(19):2165-2170
Ovarian cysts are one of the most common gynecological diseases,and laparoscopic surgery has been considered as the main approach for treating benign ovarian tumors.Laparoendoscopic single site surgery(LESS)is favored by women due to its hidden scar in the umbilicus.Combining single-port laparoscopy with open surgery(OPEN)can enhance aesthetic outcomes,reduce surgical complexity,and preserve ovarian function better.The concept of LESS-OPEN pioneered by our team in China has shown significant efficacy in treating ovarian cysts.We also pioneered the construction of a feasibility prediction scoring system for laparoendoscopic single-site extracorporeal(LESS-E)ovarian cystectomy,and established an indication system for LESS-E surgery for ovarian cysts to guide surgeons in selecting surgical approaches.This paper aims to discuss the application of the LESS-OPEN technique in ovarian cystectomy and to explore its future prospects.
4.Advances in HPV self-sampling for cervical cancer screening
Yan XU ; Yanni ZHU ; Xueju WU ; Yanzhou WANG
International Journal of Laboratory Medicine 2024;45(18):2264-2269
Cervical cancer is the fourth most common cancer among women worldwide,and several screen-ing methods are currently available,with DNA testing for human papillomavirus(HPV)considered to be the most effective technique compared to other screening methods.However,due to the lack of organized screen-ing programs and facilities in developing countries,effective screening of cervical cancer is difficult to imple-ment,thereby delaying disease prediction and contributing to the high incidence of cervical cancer.In order to improve cervical cancer screening coverage in women,a simple,time-saving and non-invasive screening method is needed.At present,more and more evidence supports the validity and practicability of self-sampling as an al-ternative method for primary HPV screening.In this paper,we reviewed the application progress of HPV self-sampling in cervical cancer screening from three aspects:vaginal self-collection,initial urine sample self-collec-tion and menstrual blood sample self-collection.
5.Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy
Dan ZHOU ; Yudi LI ; Kaijian LING ; Ruiwei WANG ; Yanzhou WANG ; Shuai TANG ; Zhiqing LIANG
Chinese Journal of Obstetrics and Gynecology 2023;58(1):49-59
Objective:To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths.Methods:The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results:(1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer ( P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage ( HR=1.882, 95% CI: 1.305-2.716), LNM ( HR=2.178, 95% CI: 1.483-3.200) and UCI ( HR=3.650, 95% CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage ( HR=2.500, 95% CI: 1.580-3.956), LNM ( HR=2.053, 95% CI: 1.309-3.218), UCI ( HR=3.984, 95%C I: 1.917-8.280), PVM ( HR=3.235, 95% CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% ( P=0.794), and the 5-year OS were 90.8% and 89.3% ( P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions:Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.
6.First report of invasive Pomacea snails in Shandong Province
Long-jiang WANG ; Yan XU ; Hui SUN ; Ben-guang ZHANG ; Xiang-li KONG ; Hai-tao HAN ; Jin LI ; Yue-jin LI ; Li-min YANG ; Yun-hai GUO ; Yong-bin WANG
Chinese Journal of Schistosomiasis Control 2022;34(4):407-411
Objective To characterize the species of invasive Pomacea snails that were discovered for the first time in Shandong Province. Methods Pomacea snails samples were collected in the field of Jining City, Shandong Province on October 2021 for morphological identification. Pomacea snails were randomly sampled and genomic DNA was extracted from foot muscle tissues of Pomacea snails for multiplex PCR amplification. The PCR amplification product was sequenced. Then, the sequence was aligned and a phylogenetic tree was created using the software MegAlign 7.1.0. In addition, Angiostongylus cantonensis infection was detected in Pomacea snails with the lung microscopy. Results A total of 104 living Pomacea snails were collected, and all were characterized as Pomacea spp. based on morphological features. Of 12 randomly selected adult Pomacea snails, multiplex PCR assay and sequencing identified eleven snails as P. canaliculata and one as P. maculata. No A. cantonensis infection was detected in 104 Pomacea snails. Conclusion This is the first report of invasive Pomacea snails in Shandong Province, where P. canaliculata and P. maculata are found.
7.Analysis of early treatment of 12 cases with congenital knee dislocation
Zhenxing LIU ; Ting LI ; Huitao QI ; Xing WANG ; Yanzhou WANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(20):1563-1566
Objective:To investigate the curative effect of the Pavlik harness and polyester material casting bandage for the early treatment of congenital knee dislocation (CDK).Methods:The clinical data of 12 patients (13 knees) with CDK treated in Provincial Hospital Affiliated to Shandong First Medical University from December 2011 and January 2019 were studied retrospectively.There were 3 males and 9 females.The median age at the initial visit was 3 days ( 1-29 days). Eleven patients had unilateral CDK, and 1 patient had bilateral CDK.There were 5 cases(5 knees) with dislocation and 7 cases(8 knees) with subluxation.Associated musculoskeletal anomalies were observed in 7 patients, which included developmental dysplasia of the hip (DDH) in 6 patients, bilateral DDH and right clubfoot in 1 patient.The Pavlik harness was applied to keep the knee in position for 1.5-2.0 months if passive flexion achieved 90°or more.If passive flexion was below 90°, the polyester material casting bandage was employed to increase knee flexion, and the bandage was changed once a week.After passive flexion reached 90°, the patient was treated with the Pavlik harness for 1.5-2.0 months.Cases with DDH who worn the Pavlik harness were evaluated by ultrasonography in the follow-up period, and cases with clubfoot were treated with Ponseti polyester material casting bandages.Results:Three children (4 knees) were directly fixed with Pavlik harness for 1.5-2.0 months, 9 children (9 knees) were fixed with Pavlik harness for 1.5-2.0 months after 1-8 times (average 2.9 times) of plaster fixation. No plaster and Pavlik harness complications were found during the treatment.Twelve patients were followed up for 29.8 months on average (12.0 to 65.0 months). Ten patients (11 knees) were rated excellent, and 2 patients (2 knees) were rated good.Conclusions:The Pavlik harness and polyester material casting bandage for early treatment of CDK is simple, effective and safe.Associated musculoskeletal anomalies can also be corrected in the treatment process.The knee joint dislocation should be treated at first.
8.A prospective multicenter cohort study comparing vNOTES and laparoscopic sentinel lymph node mapping for endometrial cancer
Li DENG ; Keyao CHEN ; Yuan DENG ; Shuai TANG ; Li SUN ; Yanzhou WANG
Journal of Gynecologic Oncology 2022;33(S1):S7-
Objective:
To determine the feasibility and safety of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) in hysterectomy and sentinel lymph node (SLN) mapping for endometrial cancer by comparing its SLN detection rate and perioperative outcomes with those of laparoscopic staging.
Methods:
In this multicenter prospective cohort study, 68 patients with early endometrial cancer between 2020 and 2021 in 2 tertiary referral centers in China were grouped to vNOTES (n=33) or laparoscopy (n=35). All the patients underwent hysterectomy with SLN mapping.
Results:
The total successful SLN detection was 97.0% in the vNOTES group and 91.4% in the laparoscopy group (p=0.32), whereas the bilateral success rates were 81.8% and 80.0%, respectively (p=0.84). There was no difference in SLN detection observed between the 2 groups regarding the side-specific mapping efficacy quotient (89.4% vs 85.7%; p=0.05). The number of harvested SLNs, the location of SLNs, operative time, estimated blood loss, intraoperative and postoperative complications and hospital cost in the 2 groups were similar (p>0.05), but there were differences in the 2 groups; the one was postoperative exhaust time that was 18 vs. 21 hours (p=0.01), the other was median postoperative hospital stay which was 4 vs. 5 days (p=0.05).
Conclusion
This study suggests that lymph node mapping can be completed through the vNOTES procedure. It can ensure effective surgical staging and show the advantages of a fast recovery and good cosmetic effect.
9.Establishment and application of a nomogram model for prognostic risk prediction in patients with epithelial ovarian cancer
Zhen LI ; Xiongwei CAI ; Ping YAN ; Dan ZHOU ; Mingmin HE ; Li DENG ; Yanzhou WANG ; Zhiqing LIANG
Chinese Journal of Obstetrics and Gynecology 2022;57(3):190-197
Objective:To explore the prognostic factors of epithelial ovarian carcinoma (EOC), construct a nomogram model, and evaluate the prognosis of EOC patients.Methods:A retrospective analysis was performed on clinicopathological data of 208 cases of EOC patients who received initial treatment in the First Affiliated Hospital of Army Medical University from August 11, 2016 to July 11, 2018, including age, preoperative ascites, preoperative neoadjuvant chemotherapy, surgical method, pathological type, pathological differentiation degree, surgical pathology stage, preoperative and post-chemotherapy serum cancer antigen 125 (CA 125) level, human epididymal protein 4 (HE4) level, platelet count and platelet/lymphocyte number ratio (PLR). The univariate and multivariate Cox risk ratio models were used to analyze the related factors affecting progression free survival (PFS) in EOC patients, and the prediction nomogram of PFS in EOC patients was established to evaluate its efficacy in predicting PFS. Results:Univariate analysis showed that preoperative neoadjuvant chemotherapy, pathological type, pathological differentiation degree, surgical pathology stage, serum CA 125 and HE4 level before operation and after chemotherapy, platelet count and PLR before operation and after chemotherapy were significantly correlated with PFS in EOC patients (all P<0.05). Multivariate analysis showed that surgical pathology stage, preoperative PLR, serum CA 125 and HE4 level after chemotherapy were independent prognostic factors affecting PFS of EOC patients (all P<0.01). The index coefficient of the prediction model for the prognosis of EOC patients established by this method was 0.749 (95% CI: 0.699-0.798), which had good prediction ability, and could help clinicians to more accurately evaluate the prognosis of EOC patients. Conclusion:The nomogram model constructed based on surgical pathology stage, preoperative PLR, serum CA 125 and HE4 level after chemotherapy could effectively predict the PFS of EOC patients after initial treatment, could help clinicians to screen high-risk patients, provide individualized treatment, and improve the prognosis of EOC patients.
10.The value of MRI anterior cartilaginous acetabulum-head-index to evaluate hip function after treatment of developmental dysplasia of the hip
Wenshuang ZHANG ; Yanzhou WANG ; Tianyou LI ; Cong SUN ; Qinhua LUAN ; Yongguang BAN ; Yufan CHEN ; Aocai YANG ; Ye LI ; Guangbin WANG
Chinese Journal of Radiology 2021;55(10):1076-1081
Objective:To evaluate the feasibility of high resolution MRI for the measurement of anterior cartilaginous acetabulum-head-index (A-CAHI) and the value of A-CAHI for predicting hip clinical function after treatment in developmental dysplasia of the hip (DDH).Methods:The imaging data of 92 hips from 61 children with treated DDH were retrospectively reviewed in Shandong Medical Imaging Research Institute from January 2019 to January 2020. All children underwent conservative treatments or surgical interventions 3 years ago. Hip function after treatment was evaluated clinically based on the modified MacKay criteria. The hips were divided into satisfactory clinical function group (McKay rating excellent or good, n=46) and unsatisfactory group (McKay rating fair or poor, n=46). All patients were imaged with conventional MRI, high resolution fat suppressed proton density weighted image (FS-PDWI) of the unilateral hip joint in oblique sagittal view, and anteroposterior hip radiographs. A-CAHI and lateral cartilaginous acetabulum-head-index (L-CAHI) were measured respectively on high-resolution oblique sagittal PDWI and conventional coronal T 1WI. Acetabulum head index (AHI) was also measured on anteroposterior hip radiograph. Mann-Whitney U test or independent-samples t test was used to compare the difference of A-CAHI, L-CAHI and AHI between satisfactory and unsatisfactory clinical function groups. The diagnostic value using A-CAHI, L-CAHI, AHI, or A-CAHI combined with L-CAHI for unsatisfactory clinical function were investigated by the ROC curve. The area under the curve (AUC) and the Z statistic were used to compare diagnostic performance. Results:The values of A-CAHI, L-CAHI and AHI were significantly higher in satisfactory clinical function group compared with the unsatisfactory group ( Z=-7.746, -7.735, t=-7.199, all P<0.001).A-CAHI combined with L-CAHI had the significant highest diagnostic accuracy compared with A-CAHI, L-CAHI and AHI (AUC were 0.994, 0.969, 0.968, 0.861, respectively), with significant differences ( Z=1.975, 2.006, 3.553, P=0.048, 0.051,<0.001). The sensitivity and specificity of A-CAHI combined with L-CAHI for the diagnosis of prognosis were 95.7% and 97.8%, respectively. Conclusions:A-CAHI measured by high resolution MRI was found to have the highest diagnostic accuracy for prediction of hip clinical function in the treated DDH, and combined with L-CAHI can improve the diagnostic accuracy significantly.

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