Objective:To analyze the prevalence of malnutrition among human immunodeficiency virus-exposed uninfected (HEU) children and to identify the associated factors in Hunan Province.Methods:All children born to human immunodeficiency virus (HIV)-infected mothers retrieved from Information System of Prevention of Mother-to-Child Transmission of human immunodeficiency virus Management (IPMTCT) in Hunan Province between July 2013 and June 2019 were included. Information including maternal demographic characteristic, maternal comorbidities/complications, anti-retroviral therapy during pregnancy, anti-retroviral prophylaxis for children, birth weight, and disease during follow-up was collected. The length and weight of children at one, three, six, nine, 12 and 18 months of follow-up time points were detected, and the prevalences of stunting, underweight, wasting and malnutrition among HEU children were evaluated. The generalized estimating equation was used to fit the logistic regression model to analyze the associated factors for malnutrition.Results:A total of 656 HEU children were finally included. The prevalences of stunting, underweight, wasting, and malnutrition among HEU children were highest at one month of age, which were 11.9%(78/656), 9.1%(60/656), 7.0%(45/656) and 21.0%(138/656), respectively. Maternal comorbidities/complications (adjusted odds ratio (a OR)=2.30, 95% confidence interval ( CI) 1.48 to 3.58), mono/dual anti-retroviral therapy during pregnancy (a OR=2.38, 95% CI 1.54 to 3.68), birth weight <2 500 g (a OR=2.66, 95% CI 1.69 to 4.21) and disease during follow-up (a OR=1.73, 95% CI 1.10 to 2.70) were the risk factors for malnutrition among HEU children (all P<0.050). Both taking zidovudine (a OR=0.60, 95% CI 0.38 to 0.94) and nevirapine (a OR=0.31, 95% CI 0.18 to 0.52) for anti-retroviral prophylaxis were the protective factors for malnutrition among HEU children (both P<0.050). Conclusions:The prevalence of malnutrition among HEU children is high. The prevalence of malnutrition is affected by maternal comorbidities/complications, anti-retroviral therapy during pregnancy, and birth weight, diseases during follow-up and anti-retroviral prophylaxis for children.

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 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 assess the treatment and prognosis of vulvar melanoma.Methods:A total of 59 cases of primary vulvar melanoma admitted to Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1st, 1981 to November 30th, 2019 were collected. The clinical characteristics, treatment, survival and prognostic factors of vulvar melanoma were analyzed retrospectively. The end date of follow-up was January 15th, 2020.The median follow-up time was 26.0 months (range:2-198 months).Results:(1) Clinical characteristics: the median age of 59 patients with vulvar melanoma was 56 years old (range:18-83 years old). According to the American Joint Committee on Cancer stage manual, there were 18, 7, 26 and 8 cases of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. The lesion of 38 cases was single and the other 21 cases were multiple. The largest diameter of the tumor ranged from 0.3 to 17.0 cm.The surface of the lesion was ulcerated in 17 cases. (2) Treatment: a total of 59 cases with vulvar melanoma, 56 patients received surgery, 36 cases of them received radical resection of vulva and 20 received local extended resection of vulvar tumor due to unilateral vulva lesion. Three patients did not receive surgery,one received chemotherapy combined with interferon, one received interferon, and one received radiotherapy. Lymph node management: among the 56 patients treated by surgery, 37 patients received inguinal lymphadenectomy, 24 (65%, 24/37) of whom were confirmed with inguinal lymph node metastasis by postoperative pathological examination. Inguinal lymph nodes enlargement were not found in 19 cases by preoperative imaging and clinical examination. In these 19 patients, three patients received inguinal lymph node biopsy, among them, one (1/3) patient was confirmed with inguinal lymph node metastasis by postoperative pathological examination, and the remaining 16 patients did not receive inguinal lymph node surgery. Postoperative adjuvant treatment: among the 56 patients who received surgery, 31 received adjuvant chemotherapy，one received adjuvant radiotherapy, four received interferon therapy, 17 received combination therapy including chemotherapy, and three did not receive postoperative adjuvant therapy. (3) Survival:during the follow-up period, the median survival time of 59 patients with vulvar melanoma was 30.0 months (range:2.0-198.0 months). The 3-year survival rate was 42.5%, and the 5-year survival rate was 23.8%. The median survival time of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 72.0, 45.0, 24.0 and 23.0 months, respectively. The difference among stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ were statistically significant （ P<0.01）. The median survival time of patients undergoing radical resection of the vulva (35.0 months) and local enlarged tumor resection (29.0 months) were significantly longer than that of patients without surgery (9.0 months, P<0.01). The median survival time of the patients who underwent inguinal lymphadenectomy, lymph node biopsy and those who did not undergo surgery were 35.0, 32.0 and 30.0 months, respectively. There were no significant differences among the 3 groups ( P>0.05). The median survival time of postoperative adjuvant chemotherapy patients (49.0 months) were significantly longer than that of postoperative adjuvant radiotherapy, interferon,and combination therapy including chemotherapy (9.0, 14.0 and 26.0 months, respectively, all P<0.01). (4) Prognostic factors: the univariate analysis showed that stage, vulvar operation and postoperative adjuvant treatment were the risk factors affecting the prognosis of patients with vulvar melanoma ( P<0.01). Multivariate analysis revealed that stage alone was an independent risk factor affecting the prognosis of patients with vulvar melanoma ( P<0.01). Conclusions:The prognosis of patients with vulvar melanoma is poor, and stage is an independent prognostic factor.Surgery combined with postoperative adjuvant chemotherapy may achieve relatively good results.

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.

Objective: To investigate the clinicopathological features and risk factors in patients with mucinous borderline ovarian tumors (MBOT). Methods: From 1999 to 2006, 66 MBOT patients in our hospital with more than ten-year follow-up were enrolled retrospectively. They were re-classified according to the literature. The clinicopathological features of different subgroups, including age, preoperative serum tumor markers, surgical methods, pathological features, surgical pathology staging, as well as the risk factors of recurrence and survival were analyzed. Results: Median age was 39 years in 66 patients. Before the surgery, 33.3% (20/60) patients had elevated CA125 and 51.7% (30/58) had elevated CA199. The accurate rate for fast frozen pathology of resected specimen was 73.4%. 21 patients underwent conservative surgery and 45 patients underwent extensive surgery. 57 patients underwent comprehensive operation and 43 cases (75.4%) resulted in stage Ⅰ. 48 of the 66 patients (72.7%) had intestinal-type tumors (IMBT) and 18 patients (27.3%) had endocervical-like tumors (EMBT). The median follow-up was 150 months. Eight recurrences (12.1%) were identified. The mean time between surgery to the initial recurrence was 26.4 months (13 to 50 months). Recurrence rate of IMBT was higher than that of EMBT (14.6% versus 5.6%) with no significance (P>0.05). All patients with pseudomyxoma had disease recurrence. Recurrence rate of stage Ⅲ patients was significantly higher than that of stage Ⅰ patients (33.3% versus 9.3%, P<0.05). During the follow-up period, tumor-related death occurred in 2 cases with a 10-year survival rate of 95.4%. Kaplan-Meier method and Log Rank analysis showed that clinical staging and peritonealmyxoma were adverse prognostic factors (P<0.05). Although the recurrence rate of patients undergoing conservative surgery was higher than that of patients with extensive surgery (23.8% versus 6.7%, P=0.047), the overall survival was almost the same between these two groups (P>0.05). Conclusions MBOT patients have relatively good prognosis. IMBT are more common than EMBT subtypes, but recurrence rate and patient survival were almost the same between these two groups. Patients with pseudomyxoma was more likely to have disease recurrence. Patients who underwent conservative surgery resulted in higher recurrence rate but did not affect the overall survival of patient. Pseudomyxoma and clinical staging were adverse prognostic factors in MBOT patients.

Objective To investigate the clinical features, treatments and prognostic factors of rhabdomyosarcoma (RMS) in the female genital tract. Methods A retrospective analysis was performed on 13 cases of RMS in the female genital tract. Clinical characteristics, treatments and prognosis were compared and analyzed statistically. Results The median age was 21.0 years (range, 6 to 54 years). There were 6 cases vaginal RMS and 7 cases cervical RMS, included 11 cases of embryonal RMS (ERMS) and 2 cases of alveolar RMS (ARMS). According to the Federation International of Gynecology and Obstetrics (FIGO)staging system,there were 6 cases of stageⅠ, 3 cases of stageⅡ, 1 case of stageⅢand 3 cases of stage Ⅳ, the median survival time were respectively 112.5, 153.0, 9.0 and 3.5 months. According to the Intergroup Rhabdomyosarcom Study Group (IRSG) staging system, there were 10 cases of stageⅠ and 3 cases of the stage Ⅳ, and their median survival time were respectively 112.5 and 3.5 months. Nine patients received surgery and the median survival time was 108.0 months (range, 9 to 228 months), 6 of them received chemotherapy after surgery and the median survival time was 152.0 months (range, 9 to 228 months), the other 3 cases did not receive any therapy after surgery and the median survival time was 25.0 months (range, 9 to 108 months). Four patients did not receive surgery and the median survival time was 6.3 months (range, 1 to 117 months). There were 2 cases received combined treatment included radiotherapy and the survival time were respectively 4 and 198 months. There were 8 cases who was survival without disease and 5 cases died of cancer. The median survival time in 13 patients was 25.0 months (range, 1 to 228 months) and the 5-year overall survival rate was 58.6%. Conclusions The prognosis of early stage of RMS in the female genital tract is good. While, the prognosis of advanced stage is poor. The standard treatment strategy is combination of surgery and chemotherapy,whether radiotherapy could improve the prognosis still need further study.

Objective To evaluate the impacts of slice thickness and registration frame range on the accuracy of cone-beam computed tomography ( CBCT) image-guided head and neck ( HN) radiotherapy, and to provide a basis for positioning correction in image-guided radiotherapy.Methods A planned CT scan was performed for an anthropomorphic HN phantom with slice thickness of 1 mm and 3 mm and simulated positioning errors in x, y, and z directions on the accelerator.CBCT scan and reconstruction were performed with slice thickness of 1 mm and 3 mm.Two different registration frame ranges were used ( range 1:from C7 to superior orbit;range 2:from C7 to calvaria ) .Automatic bony registration was performed for CBCT and planned CT images with slice thickness of 1 mm and 3 mm.The registration accuracy was evaluated.Results For range 1, the registration errors in x, y, and z directions with a slice thickness of 1 mm were significantly lower than those with a slice thickness of 3 mm (0.5±0.2 mm vs.-0.7±0.2 mm, P=0.00;0.5±0.3 mm vs. 1.0±0.3 mm, P=0.00;-0.1±0.5 mm vs.1.5±0.5 mm, P=0.00).For range 2, the registration errors in x, y, and z directions with a slice thickness of 3 mm were-0.4±0.2 mm, 0.5±0.2 mm, and 0.7±0.4 mm, respectively.Conclusions Engagement of calvaria in registration range can substantially enhance the registration accuracy in CBCT or CT images for HN.The registration error with slice thickness of 1 mm can be controlled within 1 mm.

Objective To evaluate the accuracy of image registration based on bony structure (RBS) and grey-scale (RGS) in positioning correction of radiation treatment,and their reliability in clinical application.Methods Setup errors of anthropomorphic phantom (chest& abdomen,head& neck) were simulated with x-,y-,z-directions.CBCT images were acquired for each simulation and registered with planning CT.using bony structure and grey-scale registration separately.Geometry accuracy of all registration were then obtained and analyzed.Results The errors of RBS and RGS in x-,y-,z-directions were (-0.65 ±0.22) mm and (-0.70±0.17) mm (P=0.00),(1.02 ±0.27) mm and (0.90±0.20) mm (P =0.00),(1.46 ± 0.53) mm and (1.47 ± 0.47) mm (P =0.54) for head& neck positioning; with (0.82±0.33) mm and (0.79±0.18) mm (P=0.03),(2.45±1.17) mm and (1.61 ±0.84) mm (P =0.00),(1.44 ± 3.25) mm and (0.19 ± 1.11) mm (P =0.00) for chest& abdomen positioning.Conclusions RGS is more accurate and stable than RBS.The accuracy of image registration is a little better for head& neck than that for chest& abdomen.The algorithms of image registration used in clinical application needs to be tested independently and the systematic error needs to be corrected before applying in different treatment techniques according to their accuracy requirement.