[Pathological characteristics and survival analysis of 355 patients with gastroenteropancreatic neuroendocrine neoplasms].

Objective: Biological behavior, pathological characteristics and prognostic factors of 355 cases with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) were analyzed in this retrospective study. Methods: In our study, 355 patients pathologically diagnosed as GEP-NENs were identified from April 2006 to November 2017 in the Fourth Hospital of Hebei Medical University. The biological behavior, pathological characteristics and prognosis were analyzed retrospectively. Results: There were 355 patients (228 males and 127 females) with a mean age of 58.3±10.7 years. GEP-NENs were detected most frequently in the stomach (48.2%), followed by the pancreas (16.1%), colorectum (14.1%), esophagus (7.6%), duodenum/jejunum(5.6%), liver (4.2%), appendix (2.3%) and gallbladder/bile duct (2.0%). The main clinical manifestations of non-functional GEP-NENs were abdominal pain (88/350, 25.14%), ventosity (77/350, 22.00%) and dysphagia (68/350, 19.43%), which were generally lacking specificity at the first diagnosis. 295 patients were treated surgically, including 45 cases of endoscopic resection and 250 cases of laparoscopic operation. Concerning to pathological grading, there were 22.5% (80/355) patients in grade 1 (G1), 12.7% (45/355) in grade 2 (G2), and 58.9% (209/355) in grade 3 (G3). The median follow-up time was 34 months. Furthermore, the 1-, 3- and 5-year overall survival calculated by Kaplan-Meier method were 80.1%, 59.8%, and 57.5%, respectively. Univariate analysis revealed that tumor site, treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis, tumor size, preoperative leukomonocyte level and preoperative plasma albumin were associated with overall survival (all P<0.05). Multivariate analysis showed that treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis and tumor size were independent prognostic factors for GEP-NENs (all P<0.05). Conclusions: The clinicopathological characteristics of GEP-NENs should be mastered by clinicians, and the standard treatment measures were also needed to be formulated based on the prognostic factors in order to improve the prognosis of patients.

[Effect and mechanism of PRDX1 in epithelial mesenchymal transformationin of gastric cancer cells].

Objective: To explore the effect and mechanism of peroxiredoxin1 (PRDX1) in epithelial mesenchymal transformation (EMT) of gastric cancer cells. Methods: The expression of PRDX1 protein was detected by immunohistochemistry (IHC) in 70 paraffin specimens of cancer and normal mucosa adjacent to gastric cancer, and the relationship between PRDX1 protein and clinicopathological characteristics was analyzed. Then PRDX1-small interfering RNA (siRNA) was synthetized and transfected into human gastric cancer cell line AGS, and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay was used to test cell proliferation. Transwell chamber assay was employed to test invasion of cells. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were utilized to test the expressions of PRDX1, E-cadherin, N-cadherin, vimentin, and claudin-1. Results: The positive rate of PRDX1 protein expression in gastric cancer was 81.4%, higher than that in normal mucosa (27.1%, P<0.05). The expression of PRDX1 protein was related to invasive depth and lymph node metastasis of gastric cancer (P<0.05). The expressions of PRDX1 mRNA and protein in AGS cells (2.216±0.445, 1.212±0.136), were higher than those in GES-1 cells (0.342±0.041, 0.328±0.038) (P<0.05). When PRDX1-siRNA was transfected into AGS cells, the proliferation of AGS cells was significantly inhibited (all P<0.05). The invasion and migration rate of AGS cells in the transfection group [(112.00±17.98), (50.87±9.79)%] were significantly lower than those of the negative control group [(192.50±22.02), (83.03±8.67)%] and blank control group [(193.83±22.40), (82.40±7.21)%] (all P<0.05). The expressions of mRNA and protein of N-cadherin, vimentin and claudin-1 decreased, while the expression of E-cadherin increased when PRDX1-siRNA was transfected into AGS cells (P<0.05). Conclusion: PRDX1 may promote the development of gastric cancer by regulating the EMT of gastric cancer cells.

Semen quality pattern and age threshold: a retrospective cross-sectional study of 71,623 infertile men in China, between 2011 and 2017.

BACKGROUND: The aim of this study was to provide information on the semen quality pattern of infertile men and age thresholds for semen parameters in China. METHODS: This was a retrospective cross-sectional study investigating 71,623 infertile men from the Reproductive and Genetic Hospital of CITIC Xiangya in Hunan, China, from 2011 to 2017. The Kruskal-Wallis test, Mann-Kendall test, linear regression model and joinpoint regression were used. RESULTS: Although erratic changes were observed in the median semen parameters (sperm concentration 40.1-52.1 × 106/ml, total sperm count 117.8-153.1 × 106, sperm progressive motility 33.4-38.1%) during the 7 years of observation, no significant decrease in semen quality was found, and 47.88% of infertile men showed normal semen parameters according to the World Health Organization (WHO) criteria. According to the joinpoint regression analysis, sperm progressive motility appeared to decrease earlier than the sperm concentration and total sperm count (at 28, 58, and 42 years of age, respectively). CONCLUSIONS: There is no evidence of a deterioration in semen quality among infertile men in Hunan, China. Semen parameters decreased with increasing age, with turning points noted at different ages. Semen parameters are not absolute evidence for the assessment of male fertility potential. Therefore, we believe that, among semen parameters, the sperm concentration is the best predictor of fertility for ART, followed by motility. Decreased sperm motility may affect natural pregnancy, but it is not necessary for successful IVF.

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression.

Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.

[Effect of postoperative precision nutrition therapy on postoperative recovery for advanced gastric cancer after neoadjuvant chemotherapy].

Objective: To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC). Methods: 71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery. Moreover, the difference between two groups in short-term effects were evaluated. Results: The daily energy supply of control group was 30.1%-43.74% higher than that of the experimental group (P<0.05). The resting energy expenditure (REE) of the research group after surgery was lower than that before operation. The levels of prealbumin, albumin and lymphocyte count were higher in research group than the controls at the 7th day after surgery whereas the opposite was true for the creatinine, urea nitrogen, C-reactive protein and procalcitonin (P<0.05). Similarly, the rate of malnutrition and nutritional risk became lower in the research group (P<0.05). The gastrointestinal function recovery of patients in the research group was comparable to that of the control group (P>0.05). Moreover, the complication rate and hospitalization costs of in research group were significantly lower than that of in control group (P<0.05). For patients with or without nutritional risks before surgery, the nutritional index and inflammatory index in the research group were better than those in the control group. Conclusion: Postoperative precision nutrition therapy may improve the postoperative nutritional status and short-term effects of patients with AGC after NC.

[Expression of annexin A7 and its clinical significance in gastric carcinoma].

OBJECTIVE: To investigate the expression of annexin A7 (ANXA7) in the differentiation and lymphatic metastasis of gastric cancer (GC), and to investigate the relationship between ANXA7 and biological characteristics of GC. METHODS: The clinicopathological data of 124 patients with gastric cancer who underwent surgical treatment in our hospital were retrospectively reviewed and analyzed. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues. Logistic regression analysis was conducted to evaluate the association between ANXA7 expression level and differentiation of the GC. RESULTS: A total of 124 GC patients were enrolled in this study, and the expression rate of ANXA7 was 65.3% in the GC. The survival rate of ANXA7-positive patients was significantly lower than that in the patients with negative expression (P<0.001). The results of Cox regression analysis showed that the positive expression of ANXA7, submucosal confinement and pathological stage of GC were associated with poor clinical outcomes. The ratio of pixel density value of primary GC tissues with lymph node metastasis was significantly higher than those in the tissues without lymph node metastasis (0.51±0.07 vs. 0.39±0.06, P<0.001). ROC analysis showed a high area under the curve for the ratio of pixel density value of annexin A7 in the primary GC tissues. At a cut-off level of >0.419, the ratio of pixel density value of ANXA7 exhibited a sensitivity of 91.2% and a specificity of 72.7% for detecting lymph node metastasis of GC. CONCLUSION: High annexin A7 expression is associated with poor differentiation of gastric cancer, and it may become a predictor for lymphatic metastasis of GC.

Impact of Annexin A3 expression in gastric cancer cells.

Annexin A3 participates in various biological processes, including tumorigenesis, drug resistance, and metastasis. The aim of this study was to investigate the expression of Annexin A3 in gastric cancer and its relationship with cell differentiation, migration, and invasion of gastric cancer cells. Annexin A3 expression in gastric cancer tissues was detected by quantitative real-time PCR and Western blotting. The proliferation of gastric cancer cells was measured by the MTT assay. Cell migration and invasion were determined via wound healing and transwell assays, respectively. Knock down of endogenous Annexin A3 in gastric cancer BGC823 cells was performed using siRNA technology. The expression of Annexin A3 was significantly upregulated in gastric cancer tissues, and negatively correlated with the differentiation degree. Silencing of endogenous Annexin A3 suppressed the proliferation, migration, and invasion of BGC823 cells. Additionally, the expression of p21, p27, TIMP-1, and TIMP-2 was upregulated, and the expression of PCNA, cyclin D1, MMP-1, and MMP-2 decreased in cells treated with Annexin A3-siRNA. Annexin A3 was upregulated in gastric cancer cells. Deletion of endogenous Annexin A3 significantly inhibited gastric cancer cell proliferation, migration, and invasion.

ZNF139 promotes tumor metastasis by increasing migration and invasion in human gastric cancer cells.

Zinc finger protein 139(ZNF139), a member of zinc finger protein family, is a transcription factor. Our previous research showed ZNF139 was overexpressed in gastric cancer cells. The purpose of present study is to explore impact and mechanism of ZNF139 on metastasis by regulating invasive ability of gastric cancer cells. Quantitative RT-PCR(QRT-PCR) and Western blot were applied for detection of ZNF139 expression in gastric cancer tissues, adjacent cancer tissues, metastatic lymph nodes, gastric cancer cell lines SGC7901 and BGC823 and gastric epithelial cell line GES-1; siRNA specific to ZNF139 was synthesized and then transfected into gastric cancer cell line BGC823; wound healing assay and Transwell assay were used to observe impact of ZNF139-siRNA after being transfected into BGC823 on its invasion and migration; changes in expression of invasion and migration-related genes MMP-2, MMP-9, ICAM-1 and TIMP1 were detected before and after transfection. Gelatin zymogrphy assay were applied to determine the MMP activities. Statistical analysis was based on the SPSS11.5 software.Expression of ZNF139 in gastric adenocarcinoma tissues and cells was significantly higher than the expression in the adjacent cancer tissues, but lower than the expression in the metastatic lymph nodes; ZNF139 expression was present in gastric cancer cell lines, and the expression level was higher than that in normal gastric epithelial cells lines. ZNF139-siRNA significantly inhibited the invasion and migration activity of gastric cancer cell line BGC823. 48h after ZNF139-siRNA was transfected into gastric cancer cell line BGC823, expression and activity of invasion-related genes MMP-2, MMP-9, ICAM-1 mRNA and protein were significantly inhibited, while expressions of TIMP-1 mRNA and protein were significantly increased. At the same time, the gelatinase activities of MMP2 and MMP9 were decreased by ZNF139 interference.ZNF139 was overexpressed in gastric cancer cells, and the expression was further enhanced in the metastasis process. Knocking down ZNF139 expression in gastric cancer cells could effectively reduce gastric cancer cell invasion and migration ability, and this process might play a role by regulating MMP-TIMP balance.

Does sperm morphology affect the outcome of intrauterine insemination in patients with normal sperm concentration and motility?

The aim of this study was to assess the correlation of sperm morphology with the intrauterine insemination (IUI) outcome in patients with normal sperm concentration and motility. About 412 couples who underwent 908 IUI cycles were involved in the present study. A total of 110 clinical pregnancies were achieved with a pregnancy rate of 12.11% per cycle. The pregnancy rates per cycle were 7.60%, 12.67%, 13.62% and 13.13% in patients with <5%, 5-9%, 10-14% and >14% normal forms, respectively. The lowest pregnancy rate (7.60%) was obtained in the group with normal forms below 5%. However, this rate was not significantly different from other subgroups. Moreover, no pregnancies occurred in women >35 years old with normal sperm forms below 5%, in comparison with that in other subgroups of the same age. For women younger than 35 years old, no significant difference in pregnancy rate was observed in terms of different level of morphologically normal sperm. Our results show that for patients with normal sperm concentration and motility, IUI is recommended for first-line treatment when the woman is younger than 35 years, or morphologically normal sperm is ≥ 5%. IVF/ICSI should be performed when the normal forms are <5% and female age is > 35 years.

[Clinical features and prognosis of eight patients with splenic diffuse red pulp small B-cell lymphoma].

Objective: To investigate the clinical characteristics, response, and prognosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL) . Methods: Eight cases of SDRPL were diagnosed and treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between May 2017 and April 2022. Data on the clinical features, laboratory results, bone marrow and spleen biopsy results, response, and prognosis were collected and analyzed. Results: The median age at diagnosis was 54 (42-69) years. Splenomegaly and lymphocytosis were present in all cases, and PET/CT revealed normal to slightly elevated splenic FDG uptake. All cases were in stage Ⅳ, with spleen, peripheral blood, and bone marrow but no proximal lymph nodes involved. The cytoplasm of neoplastic villous cells was abundant, and splenic pathology showed that small homogenous lymphocytes permeated the splenic sinus and splenic cord, and the white pulp atrophied. Immunohistochemistry was not typical, and B-cell markers including CD19, CD20 and CD79α were positive. After a median follow up of 35.5 (4-60) months, 7 cases were alive after splenectomy with or without chemoimmunotherapy. The patient with CCND3 P284A and MYC S146L mutation developed to B-cell prolymphocytic leukemia (B-PLL) 1 month after splenectomy and died at 16 months of follow-up. Conclusion: A rare indolent B-cell lymphoma that primarily affects the elderly, SDRPL. Most patients achieved long-term survival, but the prognosis of patients who progress to B-PLL was poor.

[Neoadjuvant chemoradiotherapy combined with surgery versus direct surgery in the treatment of Siewert type II and III adenocarcinomas of the esophagogastric junction: long-term prognostic analysis of a prospective randomized controlled trial].

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.

[Application of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of locally advanced gastric cancer].

Objective: To explore the clinical significance of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of patients with locally advanced gastric cancer. Methods: Inclusion criteria: (1) cancer confirmed by gastroscopy and pathology without preoperative anti-tumor treatment; (2) no distant metastases found in preoperative imaging examinations; (3) patients without surgical contraindications and being tolerant to surgery; (4) patients were willing to undergo laparoscopic exploration and abdominal exfoliative cytology examination, and signed informed consent. A retrospective cohort study method was used to collect and analyze the clinicopathological data of 225 patients with advanced gastric cancer based on the above inclusion criteria from a prospective, multicenter, open, randomized controlled phase III clinical trial (registration No. NCT01516944) conducted between February 2012 and December 2018 in The Fourth Hospital of Hebei Medical University, including 162 males and 63 females with age ranged from 23 to 78 years old. Forty-five patients (20.0%) were classified as Borrmann type I to II, and 180 (80.0%) were classified as type III to IV. All the patients underwent laparoscopy and peritoneal lavage cytology under general anesthesia. Laparoscopic exploration sequence: left and right diaphragm→liver and spleen→parietal peritoneum→pelvic cavity→greater omentum, small intestine, mesentery→transverse colon mesentery →stomach. Contents of exploration: (1) with or without ascites; (2) whether metastatic lesions existed in the peritoneum, mesentery, omentum and Douglas pouch; (3) whether metastasis existed on the liver surface; (4) whether the gastric lymph nodes were swollen; (5) whether infiltration occurred on the gastric serosa surface; (6) whether gastric wall was stiff. The left and right subphrenic, the abdominal and pelvic peritoneum, and the mesentery were rinsed with 500 ml of sterilized normal saline. Position of the reverse Trendelenburg was used in the Douglas pouch. The peritoneal lavage fluid under the liver and spleen fossa was collected. Cytological examination was carried out for exfoliative tumor cells. Evaluation criteria: (1) peritoneal metastasis (P): P0 meant no peritoneal metastasis, P1 meant peritoneal metastasis; (2) free peritoneal cancer cells (CY): CY0 meant no cancer cells in peritoneal lavage fluid cytology, CY1 meant cancer cells in peritoneal lavage fluid cytology. The results of patients undergoing laparoscopic exploration combined with abdominal exfoliative cytology, treatment options and prognosis were analyzed. Kaplan-Meier method was used to calculate the survival rate and a survival curve was drawn. Log-rank test was used for survival analysis. Results: After laparoscopic exploration in 225 patients, clinical staging was corrected in 68 (30.2%) patients, of whom 7 (3.1%) downstaged and 61 (27.1%) increased in staging. Of 164 patients evaluated as P0CY0 after the first laparoscopy and peritoneal cytology examination, 126 underwent radical D2 surgery, and the other 38 patients were found to have later local lesions or extensive fusion of local lymph nodes, so then received neoadjuvant chemotherapy. Twenty-nine patients evaluated as P1CY0 or P1CY1 and 32 patients as P0CY1 underwent intraperitoneal hyperthermic chemotherapy+conversion therapy, and then a second laparoscopic exploration was performed to determine the treatment plan. In total, the original treatment regimens were changed after laparoscopic exploration in 99(44.0%) cases. The follow-up period ended in January 2019. The overall 2-year survival rate of 225 patients was 64.0%. As for those who were evaluated as P0CY0, P0CY1 and P1CY0-1 after the first laparoscopic exploration, the 2-year overall survival rate was 70.7%, 65.6% and 24.1%, respectively (P=0.002). The stratified analysis showed that among 180 patients with stage III tumor, after laparoscopic exploration combined with abdominal exfoliative cytology, 125 patients were found to be P0CY0, 28 were P0CY1, and 27 were P1CY0-1, whose 2-year overall survival rates were 70.4%, 64.3%, and 29.6% respectively, and the difference among these 3 groups was statistically significant (P=0.009). Conclusion: Laparoscopic exploration combined with abdominal exfoliative cytology in patients with locally advanced gastric cancer has important clinical guiding significance in improving accurate staging, treatment options and prognosis evaluation, and can avoid non-therapeutic open-close abdominal surgery.

Comparative Proteomics Reveal the Association between SPANX Proteins and Clinical Outcomes of Artificial Insemination with Donor Sperm.

Semen analysis is used for diagnosing male infertility and evaluating male fertility for more than a century. However, the semen analysis simply represents the population characteristics of sperm. It is not a comprehensive assessment of the male reproductive potential. In this study, 20 semen samples from human sperm bank with distinctive artificial insemination with donor sperm (AID) clinical outcomes were collected and analyzed using a two-dimensional differential in-gel electrophoresis (2D-DIGE); 45 differentially expressed protein spots were obtained, and 26 proteins were identified. Most differentially expressed proteins were related to sperm motility, energy consumption, and structure. These identified proteins included several sperm proteins associated with the nucleus on the X chromosome (SPANX) proteins. This prospective study aimed to investigate the association between the expression levels of SPANX proteins and the AID clinical outcomes. The proteins identified in this study provided a reference for the molecular mechanism of sperm fertility and revealed a predictive value of the SPANX proteins.

Mycoplasma and ureaplasma infection and male infertility: a systematic review and meta-analysis.

The relationship between mycoplasma and ureaplasma infection and male infertility has been studied widely; however, results remain controversial. This meta-analysis investigated the association between genital ureaplasmas (Ureaplasma urealyticum, Ureaplasma parvum) and mycoplasmas (Mycoplasma hominis, Mycoplasma genitalium), and risk of male infertility. Differences in prevalence of ureaplasma and mycoplasma infection between China and the rest of the world were also compared. Study data were collected from PubMed, Embase and the China National Knowledge Infrastructure. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing and publication bias testing were also performed. A total of 14 studies were used: five case-control studies with 611 infertile cases and 506 controls featuring U. urealyticum infection, and nine case-control studies with 2410 cases and 1223 controls concerning M. hominis infection. Two other infection (U. parvum and M. genitalium) were featured in five and three studies, respectively. The meta-analysis results indicated that U. parvum and M. genitalium are not associated with male infertility. However, a significant relationship existed between U. urealyticum and M. hominis and male infertility. Comparing the global average with China, a significantly higher positive rate of U. urealyticum, but a significantly lower positive rate of M. hominis, was observed in both the infertile and control groups in China.

Effect of vascular bradykinin on pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis.

OBJECTIVE: To investigate the effect of vascular bradykinin on pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis (SAP). MATERIALS AND METHODS: Ninety male Wistar rats were randomly divided into a blank control group, an SAP group and a vascular bradykinin treatment group. The SAP model was induced by the retrograde injection of 5% sodium taurocholate in the pancreaticobiliary duct. The vascular bradykinin treatment group underwent gastrostomy, with a fine plastic tube placed in the stomach that led out of body through the abdominal wall.Vascular bradykinin was fully dissolved and administered at a dose of 20 U/kg once every 8 h. The pancreatic microcirculatory blood flow volume and velocity, microvascular permeability, hemorheology were evaluated respectively by double-channel laser Doppler flowmetry, the Evans blue leakage test, a blood rheology test instrument. RESULTS: The pancreatic microcirculatory blood flow volume and velocity in the vascular bradykinin treatment group increased gradually after 48 h compared with the SAP group, and the changes were significantly different (p < 0.05). The pancreatic microvascular permeability of the vascular bradykinin treatment group was significantly reduced after 48 h compared with the SAP group (p < 0.05). The low shear rate blood viscosity, hematocrit and erythrocyte aggregation index of the vascular bradykinin treatment group were significantly decreased after 48 h compared with the SAP group (p < 0.05). CONCLUSIONS: Vascular bradykinin can improve pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis.

Age-related changes in kappa opioid receptors in the guinea-pig brain: a quantitative autoradiographic study.

Investigation into the effect of aging on kappa opioid receptors in the brains of guinea-pigs was carried out in animals aged one, six, 24 and 36 months. Quantitative autoradiography was used to monitor the concentration of kappa receptors in various anatomic regions at five rostrocaudal levels in each age-group. Areas of high binding were found in the deep layers (laminae V, VI) of the neocortex and in the internal band of the periallocortical, dorsal agranular insular cortex. Among non-cortical areas examined, the nucleus accumbens and the substantia nigra possessed kappa binding levels equal to those seen in the deep neocortical layers. In all cases where an age-related change in the level of kappa receptors was detected, the direction of the change was one of decreased binding with advancing age. Statistical analysis of the binding data revealed that the one-month-old animal possessed the highest levels of kappa binding among all age groups examined. The vast majority of age-related changes in kappa binding levels occurred in laminae V and VI of neocortical regions. The per cent decreases (18-42%), as well as their age of onset (six to 36 months) varied in different anatomical regions. Possible mechanisms to explain the age-related decreases in kappa opioid binding are presented. The majority of the age-related decreases in kappa opioid binding are found in areas of the neocortex which are characterized by their motor, sensory and associative functions. It is within these three areas of function that diminutions in performance are most apparent in senescence.

Tissue-specific induction of 17 beta-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor alpha.

The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC on 17 beta-HSD expression, we determined (1) if expression of other members of the 17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta-HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa a full-length protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta-HSD IV antibodies and were most likely proteolytic fragments of 17 bega-HSD IV. Treatment of mice which lack a functional form of PPAR alpha with PPC, demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein was dependent on PPAR alpha expression in liver and kidney. Our results demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha-dependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.

Impaired male sexual development in perinatal Sprague-Dawley and Long-Evans hooded rats exposed in utero and lactationally to p,p'-DDE.

Although the pesticide DDT has been banned in the United States for decades, it remains at low levels in the environment. p,p'-DDE, a metabolite of DDT, was recently shown to inhibit the binding of androgens to the androgen receptor and to exert antiandrogenic effects in perinatal Long-Evans (LE) rats at a dose of 100 mg/kg/day administered to pregnant dams. In this study, we compared the effects of p,p'-DDE on male sexual development in offspring of Sprague-Dawley (SD) and LE rats. The chemical was dosed by gavage to pregnant dams at 10 or 100 mg/kg body wt from gestation day 14 to 18. The developing male rats were examined for sexual developmental landmarks, while the effects of p,p'-DDE on androgen receptor expression were evaluated in the testis and other reproductive organs. The tissue dosimetry of p,p'-DDE was also determined at different stages of development following in utero and lactational exposures. The higher p,p'-DDE dose induced a reduction in the male anogenital distance, an increase in retention of male thoracic nipples and alterations in expression of the androgen receptor in either one or both strains. A much weaker response was seen in the lower dose groups. Tissue and body fluid concentrations of p,p'-DDE were similar in the two strains in some tissues but dissimilar in others, particularly in the serum levels. Higher serum p,p'-DDE levels in the LE strain during pregnancy corresponded with an overall greater sensitivity of the LE strain to the antiandrogenic effects of p,p'-DDE. These results support the previous findings of p,p'-DDE antiandrogenicity in LE rats, extend the findings to SD rats, and suggest that the developmental effects of p,p'-DDE on male rat sexual differentiation are minimal at maternal doses below 10 mg/kg/day.

Lesioning of the nucleus basalis of Meynert has differential effects on mu, delta and kappa opioid receptor binding in rat brain: a quantitative autoradiographic study.

Opioid receptor binding was investigated in rat brain following lesioning of the nucleus basalis of Meynert (nbM). The nbM, which provides cholinergic input to the cortex, was lesioned unilaterally using ibotenic acid. The efficacy of lesioning was confirmed by the observation of a significant decrease in choline acetyltransferase (ChAT) activity in the ipsilateral prefrontal cortex. The specific laminar and regional distribution of mu, delta and kappa opioid receptor binding was quantitated in various cortical and limbic structures in the rat using autoradiography. Distinct medial to lateral gradients of mu and kappa opioid binding were observed in regions of the cerebral cortex. In the lesioned hemisphere the levels of mu, delta and kappa opioid binding were altered in localized areas of the cerebral cortex and the hippocampus. The direction of these binding changes varied with the opioid receptor type being assessed. Delta opioid binding was increased in the lateral portions of the frontal, occipital, perirhinal and retrosplenial granular cortices. Kappa opioid binding was increased in the lateral portion of the occipital cortex and in the CA3 region of the hippocampus. In contrast, mu opioid binding was decreased in the lateral portions of the frontal, entorhinal and forelimb cortices. These opioid receptor changes are discussed with respect to the interactions between the cholinergic and opioid systems, and relevance of the nbM lesion model to Alzheimer's disease.