Objective:To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma.Methods:A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel′s Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups.Results:(1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups ( Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions:Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

Early detection and intervention are key strategies to reduce mortality, increase long-term survival, and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative pro-teomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues, surrounding noncancerous tissues, and distal noncancerous tissues to identify diagnostic and prog-nostic biomarkers for HCC. In total, 22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues, respectively, compared with the distal non-cancerous tissues. Among these proteins, carbonic anhydrase Ⅱ (CA2) was identified to be signifi-cantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after rad-ical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall sur-vival. Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway. Taken together, this study identi-fied a novel biomarker for HCC diagnosis and prognosis, and provided a valuable resource of HCC secretome for investigating serological biomarkers.

Mechanical thrombectomy is the most effective method for the treatment of adult acute ischemic stroke caused by occlusion of large blood vessels. Compared with traditional therapy, the curative effect is greatly improved. The evidence-based medicine evidence of the treatment is sufficient, and the efficacy is safe and reliable. Since 2015, it has been recommended by the guidelines of various countries. In 2018, the time window of mechanical thrombectomy has been extended from six hours to 24 hours, which benefits more adult patients with acute ischemic stroke. However, due to the lack of high-quality clinical research, there is no corresponding guide recommendation in children, which greatly limits its clinical application. There are some cases of mechanical thrombectomy in children and a few retrospective studies show that it is safe and effective in children in the world, but there are also some challenges. The article reviewed the challenges and implementation plan of thrombectomy in children to provide reference for clinical practice.

Objective:To build a performance evaluation index system of health project supervision for higher level of project supervision.Methods:The performance evaluation index system of project supervision was established by means of literature analysis, AHP method, and two rounds of expert consultation. In April 2019, data of health projects of both provincial and city level were collected through field investigation, and project supervision institutions were evaluated by means of weighted comprehensive scoring method, TOPSIS method and rank sum ratio.Results:The system was established with 7 level-1 indexes, 17 level-2 indexes and 42 level-3 indexes. Empirical results showed that the performance of health project supervision in Hebei province was generally stable at a high level from 2014 to 2018, yet with rooms of improvement in supervision technology and policy translation.Conclusions:Health project supervision in Hebei province should keep up with the forefront of performance management policy to explore new horizons, and establish the project fund management system study based on fiscal authorization and expenditure liability, and to enhance technical means in supervision, so as to improve supervision efficiency in the meantime of " burden alleviation" .

Objective To provide experimental materials for exploring the function of breast cancer susceptibility gene 2(BRCA2) gene by establishing of an mouse immortalized mammary gland epithelial cell line as a cell model system.Methods In this study,the primary mouse mammary epithelial cells were isolated and purified by enzyme digestion and differential centrifugation.The resulting primary mouse mammary gland epithelial cells were transducted with lentivirus expressing human telomerase (hTERT) gene,and screened by hygromycin B.The surviving epithelial cells were further characterized by morphology observations and cytokeratin marker detection.Results Immortalized mouse mammary epithelial cells were obtained by infection of MMECs with lentivirus expressing human telomerase(hTERT) gene,screened by hygromycin B.Morphology observations and detection of the cytokeratin marker showed the immortalized MMECs had a typical morphology of luminal epithelial cells with strong expression of cytokeratin 14.Conclusion An immortalized mouse luminal epithelial cell line is successfully established with an uniform morphology,which provides a cell model system for the future exploration on BRCA2-related tumorigenesis.

Knee osteoarthritis (KOA ) is a common chronic degenerative disease in the elderly population .It is character-ized by knee-joint pain ,swelling ,morning stiffness and seriously affects the patients′motor function and physical health .So far ,there is no early diagnosis and effective treatment for it .This paper outlined the recent researches on knee osteoarthritis and inflammatory cytokines to discuss the relationship between knee osteoarthritis and inflammatory factors such as IL-1β,IL-6 ,TNF-α,TGF-β,IL-10 ,IL-17 and IL-37 ,and provide the theoretical basis for the diagnosis and treatment of knee osteoar-thritis .

Objective The aim of this study is to explore the mechanism of canonical Wnt signaling pathway in type 2 diabetes mice peripheral neuropathy. Methods Male C57BL6 mice were randomly assigned to three groups. One group treated with normal diet as control. And the rest were used to establish the diabetic model through the combination of 60 kcal% high fat diet and an administration of multipleand low dose of streptozotocin on 5 consecutive days. When the model of type 2 diabetes mice peripheral neuropathy was successfully established, one group was injected with the canonical Wnt signaling pathway inhibitor XAV 939 ( T2DM-XAV 939 group) and the other one was injected with phosphate buffer saline (PBS) as control (T2DM-PBS group). The 21stweek was the end point of the experiment, and fasting blood glucose, insulin level, homeostasis model assessment for insulin resistance (HOMA-IR), plantar test, and exercise tolerance were measured, realtime PCR were adopted to detect the related mRNA expression of the canonical Wnt signaling pathway. Results T2DM-XAV 939 group had higher total cholesterol, triglyceride, fasting blood glucose, and HOMA-IR than T2DM-PBS group, but showed no statistical difference. The enzymatic activity of glutamic oxaloacetic transaminase was lower level than that in T2DM-PBS group (P＜0.05); T2DM-XAV 939 group had significantly higher plantar test and poorer exercise tolerance than those in T2DM-PBS group (P＜0.05). The mRNA levels of genes in canonical Wnt signaling pathway such as β-catenin, c-myc, mitochondrial transcription factor A (TFAM) had slightly lower level than those in T2DM-PBS group, without statistical difference, and the protein expression of c-myc was lower than that of T2DM-PBS group (P＜0.05). The insulin receptor substeate 2 (IRS-2) mRNA expression was higher than that in T2DM-PBS group (P＜0.05). With the development of the experiment, we found that the survival rate of the T2DM-XAV 939 group was significantly reduced compared with the other groups. Conclusion Inhibition of the canonical Wnt signaling pathway may aggravate diabetic peripheral neuropathy.

Objective To investigate the role of regulatory B cells (Breg)in children with newly diagnosed immune thrombocytopenia (ITP).Methods A total of 35 newly diagnosed ITP children admitted to the Pediatric De-partment,the First Affiliated Hospital of Zhengzhou University from January to December 201 4 were recruited in this study,and another 20 gender -and age -matched healthy children from the Department of Medical Examination Center of the same Hospital were recruited as controls during the same period.Peripheral blood samples (3 mL from each chil-dren)were collected from all the newly diagnosed ITP children and the normal controls.Breg cells were tested by Flow Cytometry,and the expression levels of interleukin -1 0 (IL -1 0)and transforming growth factor -β1 (TGF -β1 ) mRNA were measured by real time fluorescence quantitative polymerase chain reaction.Meanwhile,the correlation be-tween Breg cells and the expression levels of IL -1 0,TGF -β1 mRNA were analyzed by Pearson correlation.Results The percentages of Breg cells in the peripheral blood of the newly diagnosed ITP children [(2.37 ±0.67)%]were sig-nificantly lower than those of the normal controls [(4.92 ±1 .32)%],and there was a significant difference (t =-7.47,P =0.000);the expression levels of IL -1 0 mRNA in the newly diagnosed ITP children(0.202 ±0.059) were significantly decreased compared with those of the normal controls(0.41 5 ±0.21 2),and there was a significant difference(t =-5.1 75,P =0.000);while the expression levels of TGF -β1 mRNA in the newly diagnosed ITP chil-dren(1 .587 ±0.823)were significantly increased than those in the normal controls(0.61 9 ±0.322),and there was a significant difference(t =4.081 ,P =0.001 ).There was a significant positive correlation between Breg cells and the ex-pression levels of IL -1 0 mRNA(rs =0.828,P <0.05),but no correlation between Breg cells and expression level of TGF -β1 mRNA was found (rs =0.527,P =0.1 1 7).Conclusions The decrease expressions of Breg cells can be found in the newly diagnosed ITP children,and the abnormal expression of Breg cells may play a key role in the immu-nological pathogenesis of the newly diagnosed ITP children.

OBJECTIVETo observe the changes in subgingival microflora before and after Er:YAG laser treatment on diabetic patients with periodontitis, and to compare with the subgingival microflora of chronic periodontitis.

METHODSSubgingival plaque of 13 pairs of teeth (26 sites) was selected from type 2 diabetic patients at pretreatment, one month post-treatment, and three months post-treatment. Subgingival plaque was also obtained from 11 cases of moderate to severe chronic periodontitis with similar severity of periodontitis. The DNA of the subgingival plaque samples was extracted. Whole bacterial 16S rDNA gene fragments separated by denaturing gradient gel electrophoresis. Specific DNA bands were then chosen for retrieval and sequencing.

RESULTSThe gene sequencing results of the special DNA bands of subgingival plaque samples show that the pathogenic bacteria of both diabetic periodontitis and simple chronic periodontitis were Prevotella intermedia and Tannerella forsythia, respectively. The composition of the subgingival microflora before and after laser treatment changed. Some DNA bands, including that of Tannerella forsythia, disappeared or weakened one month after treatment. A new strip appeared, which belonged to Actinomyces sp.

CONCLUSIONThe profiles of the subgingival microflora changed after treatment, and one month was indicated as an important stage. Er:YAG laser may have an important function in delaying microflora recolonization.

Objective To observe the changes in subgingival microflora before and after Er: YAG laser treatment on dia-betic patients with periodontitis, and to compare with the subgingival microflora of chronic periodontitis. Methods Subgingival plaque of 13 pairs of teeth (26 sites) was selected from type 2 diabetic patients at pretreatment, one month post-treatment, and three months post-treatment. Subgingival plaque was also obtained from 11 cases of moderate to severe chronic periodon-titis with similar severity of periodontitis. The DNA of the subgingival plaque samples was extracted. Whole bacterial 16S rDNA gene fragments separated by denaturing gradient gel electrophoresis. Specific DNA bands were then chosen for retrieval and sequencing. Results The gene sequencing results of the special DNA bands of subgingival plaque samples show that the pathogenic bacteria of both diabetic periodontitis and simple chronic periodontitis were Prevotella intermedia and Tannerella forsythia, respectively. The composition of the subgingival microflora before and after laser treatment changed. Some DNA bands, including that of Tannerella forsythia, disappeared or weakened one month after treatment. A new strip appeared, which belonged to Actinomyces sp. Conclusion The profiles of the subgingival microflora changed after treatment, and one month was indicated as an important stage. Er: YAG laser may have an important function in delaying microflora recolonization.