Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

AIM:To investigate the protective effect of Shexiang-Tongxin dropping pills(STDP)against myo-cardial injury induced by coronary microembolization(CME)in rats,with a focus on the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.METHODS:Thirty-two Sprague-Dawley rats were randomly allocated into four groups using a random number table:sham group,CME group,STDP group,and RU.521 group,with 8 rats per group.A rat model of CME was established via the injection of embolic microspheres into the left ventricle.The rats in sham group received an equal volume of normal saline via left ventricular injection instead,those in STDP group were given STDP(40 mg/kg)by oral gavage once daily for 14 consecutive days before CME modeling,and those in RU.521 group were intraperitoneally injected with RU.521(5 mg/kg)once daily for 7 consecutive days before CME modeling.Echocardiography was performed to evaluate cardiac function 24 h after modeling.HE staining was used to observe pathological changes in myocardial tissue,and TTC staining was applied to detect myocardial infarction areas.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of interleukin(IL)-1β and tumor necrosis factor(TNF)-α.A commercial assay kit was employed to detect myocardial injury marker cardiac troponin I(cTnI).Western blot was performed to analyze the expression of cGAS-STING pathway-related proteins in cardiac tissues.RESULTS:Compared with sham group,the rats in CME group exhibited significantly impaired cardiac function and a marked increase in serum cTnI levels(P<0.05).In contrast,compared with CME group,the rats in both STDP group and RU.521 group demonstrated significant improvements in cardiac function and reductions in cTnI levels((P<0.05).Furthermore,HE staining and TTC staining revealed that the rats in CME group had loosely arranged myocardial fibers,swollen cardiomyo-cytes,and an increased myocardial infarction erea compared with sham group(P<0.05).Meanwhile,the expression lev-els of inflammatory factors IL-1β and TNF-α,as well as the relative expression of cGAS,STING and NF-κB p-p65 pro-teins were significantly increased(P<0.05).In comparison,the rats in STDP group and RU.521 group showed a signifi-cant reduction in myocardial infarction area,down-regulated expression of cGAS,STING,and NF-κB p-p65 proteins,and markedly decreased levels of IL-1β and TNF-α compared with CME group(P<0.05).CONCLUSION:STDP pre-treatment ameliorated myocardial injury,cardiac dysfunction and myocardial infarct size induced by CME.The underlying mechenism may involve the suppression of the cGAS-STING signaling pathway,thereby attenuating myocardial inflamma-tion after CME.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

AIM:To investigate the protective effect of Shexiang-Tongxin dropping pills(STDP)against myo-cardial injury induced by coronary microembolization(CME)in rats,with a focus on the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.METHODS:Thirty-two Sprague-Dawley rats were randomly allocated into four groups using a random number table:sham group,CME group,STDP group,and RU.521 group,with 8 rats per group.A rat model of CME was established via the injection of embolic microspheres into the left ventricle.The rats in sham group received an equal volume of normal saline via left ventricular injection instead,those in STDP group were given STDP(40 mg/kg)by oral gavage once daily for 14 consecutive days before CME modeling,and those in RU.521 group were intraperitoneally injected with RU.521(5 mg/kg)once daily for 7 consecutive days before CME modeling.Echocardiography was performed to evaluate cardiac function 24 h after modeling.HE staining was used to observe pathological changes in myocardial tissue,and TTC staining was applied to detect myocardial infarction areas.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of interleukin(IL)-1β and tumor necrosis factor(TNF)-α.A commercial assay kit was employed to detect myocardial injury marker cardiac troponin I(cTnI).Western blot was performed to analyze the expression of cGAS-STING pathway-related proteins in cardiac tissues.RESULTS:Compared with sham group,the rats in CME group exhibited significantly impaired cardiac function and a marked increase in serum cTnI levels(P<0.05).In contrast,compared with CME group,the rats in both STDP group and RU.521 group demonstrated significant improvements in cardiac function and reductions in cTnI levels((P<0.05).Furthermore,HE staining and TTC staining revealed that the rats in CME group had loosely arranged myocardial fibers,swollen cardiomyo-cytes,and an increased myocardial infarction erea compared with sham group(P<0.05).Meanwhile,the expression lev-els of inflammatory factors IL-1β and TNF-α,as well as the relative expression of cGAS,STING and NF-κB p-p65 pro-teins were significantly increased(P<0.05).In comparison,the rats in STDP group and RU.521 group showed a signifi-cant reduction in myocardial infarction area,down-regulated expression of cGAS,STING,and NF-κB p-p65 proteins,and markedly decreased levels of IL-1β and TNF-α compared with CME group(P<0.05).CONCLUSION:STDP pre-treatment ameliorated myocardial injury,cardiac dysfunction and myocardial infarct size induced by CME.The underlying mechenism may involve the suppression of the cGAS-STING signaling pathway,thereby attenuating myocardial inflamma-tion after CME.

Objective:To summarize the surgical treatment experience of extended thymectomy for myasthenia gravis(MG), and to explore the surgical treatment of MG.Methods:Retrospectively analyzed the clinical data of 527 MG patients undergoing extended thymectomy in our hospital from June 1996 to October 2017, including 242 males and 285 females, aged 5 to 77 years, with a mean age of(52.6±13.7) years old. The course of illness was 12 days to 18 years. There were 22 cases of hyperthyroidism, 7 cases of pure red blood cell aplastic anemia, 1 case each of hypothyroidism, irritable bowel disease, rheumatoid arthritis, ankylosing spondylitis and thrombocytopenia syndrome. There were 272 cases of MG in Osserman Ⅰ, 72 cases inⅡa, 78 cases inⅡb, 81 cases in Ⅲ, and 24 cases in Ⅳ, respectively. The muscle fatigue test and neostigmine test of all patients were positive, and the diagnosis was confirmed by chest CT examination. Meanwhile, summarize the perioperative data and postoperative follow-up.Results:3 cases died during the postoperative period, all of which were thymoma with MG, including 2 cases of Osserman Ⅲ MG and 1 case of Ⅳ MG; 15 cases of postoperative myasthenia crisis, including 2 OssermanⅡb cases, 11 Osserman Ⅲ cases and 2 Osserman Ⅳ cases, also including 7 cases of tracheotomy; 70 cases of plasma exchange, of whom 2 cases of hypotonic syndrome and 2 cases of lower extremity venous thrombosis. The postoperative pathological types were followed by thymic hyperplasia 293 cases(55.60%), thymoma 207 cases(39.28%), thymic cyst 24 cases(4.55%) and thymic atrophy 3 cases(0.57%) in descending order. 378 cases were followed up with an average follow-up of(85.9±58.5)months; MG with complete remission, partial remission, no change and deterioration accounted for 135(35.71%), 192(50.79%), 41(10.85%) and 10(2.65%)cases, respectively. Complete remission rate ranked as Osserman typeⅠ>Ⅱa>Ⅳ>Ⅱb>Ⅲ, the deterioration rate from high to low was Osserman type Ⅲ>Ⅳ>Ⅰ. 18 OssermanⅠcases showed no effects, whose preoperative course of disease> 5-10 years; 1 OssermanⅠcase was worsening who initially was diagnosed with ophthalmic MG and underwent video-assisted thoracoscopic thymectomy. The left thymus lobe was left unresected and developed 6 years later. Another operation was performed to remove the left lobe thymus, confirming the compensatory hypertrophy of the left lobe thymus. Among the worsening patients, 6 died, all of them were thymoma with MG, including 5 cases of type Ⅲ and one case of type Ⅳ. The cause of death was omyasthenia crisis(3 cases), sudden respiratory arrest after 3 months of rapid stopping of brompistigmine(2 cases)and cholinergic crisis(1 case).Conclusion:Standardized extended thymectomy is an effective method for the treatment of MG. Earlier surgery for ocular muscle type MG can effectively reduce the risk of generalization. MG with Osserman Ⅱb or higher is prone to myasthenia crisis. Comprehensive treatments should be taken to reduce MG-related risks. Myasthenia crisis can occur repeatedly in severe patients in the long term after surgery, requiring regular medication and comprehensive MG treatments.

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Objective:To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC).Methods:Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed.Results:(1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B 12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions:One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Objective:To investigate the effects of Commelina communis L. on hypoxia/reoxygenation (H/R)-induced apoptosis of myocardial cells and expression of inflammatory factors through regulating NADPH oxidase 4 (Nox4). Methods:H9c2 cells were subjected to H/R to establish the injury model. These cells were then treated with different concentrations of Commelina communis L. extract. Cell activity and apoptosis were measured by MTT method and flow cytometry, respectively. Superoxide dismutase (SOD), malondialdehyde (MDA) and lactate dehydrofenase (LDH) levels were detected. ELISA was performed to detect TNF-α, IL-1β and IL-6 levels. Western blot was used to detect the expression of Bcl-2-associated X protein (Bax), cysteine-containing aspartic protease 3 (Caspase-3) and Nox4. Real-time quantitative PCR (qPCR) was used to measure the expression of Nox4 at mRNA level. H9c2 cells were transfected with si-Nox4 and subjected to H/R. Changes in the activity and apoptosis of H9c2 cells, and the expression of SOD, MDA, LDH and inflammatory factors were observed after inhibiting Nox4 expression. H9c2 cells transfected with pcDNA3.1-Nox4 were treated with Commelina communis L. extract and subjected to H/R to evaluate the effects on the cell activity and apoptosis, as well as the expression of SOD, MDA, LDH and inflammatory factors. Results:The survival rate and SOD activity of H9c2 cells exposed to H/R were significantly reduced, but the apoptosis rate, the levels of Caspase-3, Bax protein, MDA, LDH TNF-α, IL-1β and IL-6, and the expression of Nox4 at both mRNA and protein levels were dramatically increased ( P<0.05). As with inhibition of Nox4 expression, Commelina communis L. extract at the concentrations of 10 μg/ml and 20 μg/ml could obviously increase the survival rate and SOD activity of H9c2 cells after H/R exposure, and reduce the apoptosis rate and the expression of Caspase-3, Bax protein, MDA, LDH TNF-α, IL-1β and IL-6, as well as Nox4 expression at mRNA and protein levels ( P<0.05). Overexpression of Nox4 reversed the effects of Commelina communis L. extract on promoting cardiomyocyte cell activity and SOD activity, inhibiting cell apoptosis, and downregulating the expression of Caspase-3, Bax protein, MDA, LDH, TNF-α, IL-1β and IL-6 in the H/R injury model. Conclusions:Commelina communis L. could protect against H/R-induced myocardial cell injury, improve cell activity, and inhibit cell apoptosis and the expression of inflammatory factors through regulating Nox4 expression.

Objective To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.