Objective To evaluate the therapeutic effect and application value of laparoscopy combined with holmium laser in the treatment of intrahepatic and extrahepatic bile duct stones.Methods Retrospectively analyzed the clinical data of 22 cases with intrahepatic and extrahepatic bile duct stones who treated with laparoscopy choledo-choscopy combined with holmium laser lithotripsy(the observation group),and 21 cases who treated with laparoscopy combined with choledochoscopic lithotomy(the control group).The clinical curative effect was compared between the two groups.Results In the observation group,the residual stones completely removed in 21 cases(95.4%),the mean operation time was (130 ±13)min,the intraoperative bleeding volume was (85 ±20)mL,the average hospitali-zation time was (8.3 ±2.0)days,without conversion to open surgery,no incision infection,1 case had residual stones after operation,through T tube sinus tract choledochoscopy took a stone again.In the control group,took net calculi in 13 cases(61.9%),the average operation time was (135 ±20)min,the intraoperative hemorrhage volume was (70 ± 15)mL,the average hospitalization time was (14.5 ±2)days,6 cases converted to laparotomy,incision infection in 2 cases,8 cases had residual stones after operation,through T tube sinus combined with choledochoscopy again take stone,which 2 secondary mirror lithotomy in 6 cases,3 cases of 2 stones.The differences of the two groups in stone from the net rate,conversion rate,average hospitalization time were statistically significant(χ2 =2.203,2.897,t =4.293,P =0.033,0.006,0.017).The differences of mean operation time,intraoperative hemorrhage had were not statistically significant(t =1.176,1.629,P =0.246,0.111).Conclusion It is safe,effective and minimally invasive for the treatment of intrahepatic and extrahepatic bile duct stones with holmium laser combined with endoscopic holmi-um laser.

Objective To compare and discuss the clinical application effect of the end-to-end anastomosis of pancreatic and intestinal anastomosis,binding type of pancreatic and intestinal anastomosis,end-to side pancreatic duct anastomosis and modified pancreatic duct jejunum anastomosis.Methods Collected pancreatoduodenectomy in 95 cases,the end-to-end pancreatico duodenal sleeve type anastomosis in 23 cases,binding type pancreatic enteric anastomosis in 18 cases,end to side pancreaticojejunostomy anastomosis in 28 cases,improvement of the pancreatic duct jejunum end to side anastomosis in 26 cases,compared with four groups of patients with pancreatic enteric anastomosis time and postoperative complications.Results Anastomosis time:A group (34.0 ± 4.6) min,B group (31.0±5.8) min,C group (32.0 ±6.3) min,D group (14.0 ±4.2) min(P=0.037,P＜0.05).And the incidence rate of postoperative pancreatic fistula,bile leakage,abdominal cavity or digestive tract bleeding had no significant difference (P ＞ 0.05).Improvement of the pancreatic tube jejunum end to side coincident with a low incidence of pancreatic fistula,but different pancreatic enteric anastomosis way pancreatic fistula rate difference was not statistically significant,improvement of the pancreatic duct and jejunum mucosa end side group pancreatic enteric anastomosis anastomosis time significantly shorter in the three groups,the difference was statistically significant (P ＜ 0.05).Conclusion Improvement of pancreatic duct jejunum end to side anastomosis with short operation time,low incidence of pancreatic fistula,and the operation is simple and practical,safe.

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.

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 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.

Background and objectiveIt is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG.MethodsThe Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, Patients were fol-lowed and their survival status were analyzed.Results There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5 year and 10 year OS rates were both higher in MG group (93%vs 88%; 83%vs 81%,P=0.034) respectively. The survival rate was signiifcantly higher in patients with MG when the Masaoka staging was III/IV (P=0.003). Among patients with advanced stage thymoma (stage III, IVa, IVb), the constitu-ent ratios of III, IVa, IVb were similar between MG and Non-MG group. Histologically, however, there were signiifcantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classiifcation, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were signiifcant factors, and multivariate analysis showed WHO Classiifcation, Masaoka stage, and resectability were strong independent prognostic indicators.ConclusionAlthough MG is not an independent prognostic factor, the sur-vival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.

Background and objectiveTo compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC)/the International Thymic Malignancies Interest Group (ITMIG) proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART) retrospective database.MethodsFrom 1992 to 2012, 2,370 patients in ChART database were ret-rospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR) was assessed in R0 patients. Overall survival (OS) was evalu-ated both in an R0 resected cohort, as well as in all patients (any R status). CIR and OS were ifrst analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal.Results Based on Masaoka-Koga staging system, signiifcant difference was detected in CIR among all stages. However, No survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was signiifcantly lower comparing to all other T categories (P<0.05) and there is a signiifcant difference in OS between T1a and T1b (P=0.004). T4 had the worst OS comparing to all other T categories. CIR and OS were signiifcantly worse in N(+) than in N0 patients. Signiifcant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb.Conclusion Compared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor dissemination. Further study using prospectively recorded information on the proposed TNM categories would be helpful to better grouping thymic tumors for predicting prognosis and guiding clinical management.

Background and objectiveTo evaluate the role of preoperative induction therapy on prognosis of local-ly advanced thymic malignancies.MethodsBetween 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery di-rectly atfer preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III-IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis.Results Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen pa-tients (25%) were downstaged atfer induction. Signiifcantly more thymomas were downstaged than thymic carcinomas (38.7%vs 13.9%,P=0.02). Tumors downstaged atfer induction had signiifcantly higher 5-year OS than those not downstaged (93.8%vs 35.6%,P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001), although R0 resection were similar (76.4%vs 73.3%,P=0.63). However, 5-year OS in tumors downstaged atfer induction (93.8%) was similar to those in the DS group (85.2%,P=0.438), both signiifcantly higher than those not downstaged atfer induction (35.6%,P<0.001).ConclusionOnly 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged atfer induction. Signiifcantly more thymomas were downstaged than thy-mic carcinomas (38.7%vs 13.9%,P=0.02). Tumors downstaged atfer induction had signiifcantly higher 5-year OS than those not downstaged (93.8%vs 35.6%,P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001), although R0 resection were similar (76.4%vs 73.3%,P=0.63). However, 5-year OS in tumors downstaged atfer induction (93.8%) was similar to those in the DS group (85.2%,P=0.438), both signiifcantly higher than those not downstaged atfer induction (35.6%,P<0.001).