Objective:To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus.Methods:This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A 1c (HbA 1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA 1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher′s exact test. Results:Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA 1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA 1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient -year; P=0.040]. Conclusions:With good glycemic control, URLi showed non-inferiority for HbA 1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.

Objective To analyze and diagnose the chromosomal genetic etiology of male patients with azoospermia or oligozoospermia,and investigate the clinical application value of combined detection of chromosomal karyotype and Y-chromosome microdeletion in azoospermia or oligozoospermia.Methods The clinical data and peripheral blood samples of 240 male patients with azoospermia or oli-gospermia in Luzhou district of Sichuan were collected.The karyotype analysis of peripheral blood lymphocytes were analyzed by G-ban-ding in conventional chromosomal culture.Multiplex PCR technology was used to detect Y chromosome microdeletions.Results A-mong the 240 male patients with azoospermia or oligospermia,179 cases of azoospermia and 61 cases of severe oligospermia were found.The detection rate of chromosome karyotype abnormalities was 22.92％(55/240),including 30 cases of chromosome number abnor-malities,21 chromosome structure abnormalities and 4 combined abnormalities.The detection rate of Y chromosome microdeletion ab-normalities was 10.42％(25/240)with the highest deletion rate of 7.08％for AZFc abnormalities.The combined detection rate for the abnormalities of karyotype and Y chromosome microdeletion was 30.83％(74/240),among which 6 patients showed abnormalities in both detections.The detection rate of combined detections by the two methods was higher than that of single method(x2=30.24,P＜0.001).Conclusion This study systematically reported the incidence and types of karyotypes and Y chromosome microdeletions in male azoospermia or oligospermia patients in Luzhou district of Sichuan.We suggest that the combined application of the two methods may improve the detection rate of abnormality,which provides important guidance for the etiological diagnosis of male infertility pa-tients,genetic counseling and reproductive therapy.

Objective:To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients.Methods:A single-center cohort study was carried out. Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry (SGCPR) in West China Hospital of Sichuan University. Finally, 4516 gastric cancer patients were included and were divided into three groups according to time periods (period 1 group: exploration stage of standardized surgical treatment, 2000 to 2006, 967 cases; period 2 group: application stage of standardized surgical treatment, 2007 to 2012, 1962 cases; period 3 group: optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy, 2013 to 2016, 1587 cases). Differences in clinical data, pathologic features, and prognosis were compared among 3 period groups. Follow-up information was updated to January 1, 2020. The overall follow-up rate was 88.9% (4016/4516) and median follow-up duration was 51.58 months. Survival curve was drawn by Kaplan-Meire method and compared with log-rank test. Univariate and multivariate analyses were performed by Cox proportional hazards model.Results:There were significant differences among period 1, period 2 and period 3 groups in the rates of D2/D2+ lymphadenectomy [14.4%(139/967) vs. 47.2%(927/1962) vs. 75.4%(1197/1587), χ 2=907.210, P<0.001], in the ratio of proximal gastrectomy [19.8%(191/967) vs. 16.6%(325/1962) vs. 8.2%(130/1587), χ 2=100.020, P<0.001], and in the median intraoperative blood loss (300 ml vs. 100 ml vs. 100 ml, H=1126.500, P<0.001). Besides, the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1, period 2 and period 3 groups (14 vs. 26 vs. 30, H=987.100, P<0.001). Survival analysis showed that the 5-year overall survival rate was 55.3% in period 1, 55.2% in period 2 and 62.8% in period 3, and significant difference existed between period 3 and period 1 ( P=0.004). The Cox proportional hazards model analysis showed that treatment period (period 3, HR=0.820, 95%CI: 0.708 to 0.950, P=0.008), postoperative chemotherapy (HR=0.696, 95%CI: 0.631 to 0.768, P<0.001) and mid-low gastric cancer (HR=0.884, 95%CI: 0.804 to 0.973, P=0.011) were good prognostic factors. Whereas old age (≥65 years, HR=1.189, 95%CI: 1.084 to 1.303, P<0.001), palliative resection (R1/R2, HR=1.538,95%CI: 1.333 to 1.776, P<0.001), large tumor size (≥5 cm, HR=1.377, 95%CI: 1.239 to 1.529, P<0.001), macroscopic type III to IV (HR=1.165, 95%CI: 1.063 to 1.277, P<0.001) and TNM stage II to IV(II/I: HR=1.801,95% CI:1.500~2.162, P<0.001;III/I: HR=3.588, 95% CI: 3.028~4.251, P<0.001; IV/I: HR=6.114, 95% CI: 4.973~7.516, P<0.001) were independent prognostic risk factors. Conclusion:Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model, the quality of surgery treatment and overall survival increase, and prognosis of gastric cancer patients has been improved.

Objective:To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients.Methods:A single-center cohort study was carried out. Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry (SGCPR) in West China Hospital of Sichuan University. Finally, 4516 gastric cancer patients were included and were divided into three groups according to time periods (period 1 group: exploration stage of standardized surgical treatment, 2000 to 2006, 967 cases; period 2 group: application stage of standardized surgical treatment, 2007 to 2012, 1962 cases; period 3 group: optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy, 2013 to 2016, 1587 cases). Differences in clinical data, pathologic features, and prognosis were compared among 3 period groups. Follow-up information was updated to January 1, 2020. The overall follow-up rate was 88.9% (4016/4516) and median follow-up duration was 51.58 months. Survival curve was drawn by Kaplan-Meire method and compared with log-rank test. Univariate and multivariate analyses were performed by Cox proportional hazards model.Results:There were significant differences among period 1, period 2 and period 3 groups in the rates of D2/D2+ lymphadenectomy [14.4%(139/967) vs. 47.2%(927/1962) vs. 75.4%(1197/1587), χ 2=907.210, P<0.001], in the ratio of proximal gastrectomy [19.8%(191/967) vs. 16.6%(325/1962) vs. 8.2%(130/1587), χ 2=100.020, P<0.001], and in the median intraoperative blood loss (300 ml vs. 100 ml vs. 100 ml, H=1126.500, P<0.001). Besides, the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1, period 2 and period 3 groups (14 vs. 26 vs. 30, H=987.100, P<0.001). Survival analysis showed that the 5-year overall survival rate was 55.3% in period 1, 55.2% in period 2 and 62.8% in period 3, and significant difference existed between period 3 and period 1 ( P=0.004). The Cox proportional hazards model analysis showed that treatment period (period 3, HR=0.820, 95%CI: 0.708 to 0.950, P=0.008), postoperative chemotherapy (HR=0.696, 95%CI: 0.631 to 0.768, P<0.001) and mid-low gastric cancer (HR=0.884, 95%CI: 0.804 to 0.973, P=0.011) were good prognostic factors. Whereas old age (≥65 years, HR=1.189, 95%CI: 1.084 to 1.303, P<0.001), palliative resection (R1/R2, HR=1.538,95%CI: 1.333 to 1.776, P<0.001), large tumor size (≥5 cm, HR=1.377, 95%CI: 1.239 to 1.529, P<0.001), macroscopic type III to IV (HR=1.165, 95%CI: 1.063 to 1.277, P<0.001) and TNM stage II to IV(II/I: HR=1.801,95% CI:1.500~2.162, P<0.001;III/I: HR=3.588, 95% CI: 3.028~4.251, P<0.001; IV/I: HR=6.114, 95% CI: 4.973~7.516, P<0.001) were independent prognostic risk factors. Conclusion:Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model, the quality of surgery treatment and overall survival increase, and prognosis of gastric cancer patients has been improved.

OBJECTIVETo establish the tissue response grading (TRG) system following neoadjuvant chemotherapy and to investigate its application in the gastric cancer patients who received neoadjuvant chemotherapy.

METHODSData of 30 cT3-4N0-3M0 gastric cancer cases who received neoadjuvant chemotherapy and operation from May 2017 to February 2018 at Department of Gastrointestinal Surgery, West China Hospital were analyzed retrospectively. The edema degree of gastrointestinal tract and perigastric tissues, intraoperative effusion, and fibrosis of tumor and lymph nodes bearing tissues which could be divided into 4 categories constituted the core parameters of the TRG system following neoadjuvant chemotherapy. Four categories of edema: grade 0, no obvious tissue edema; grade 1, slight tissue edema and swelling, no obvious effusion when dissecting the capsule of connective tissues; grade 2, moderate tissue edema and swelling, a few effusion when dissecting the capsule of connective tissues; grade 3, severe tissue edema and swelling with high tension on the capsule of connective tissues, tension blister could be observed in some patients, continuous effusion when dissecting the capsule of connective tissues. Four categories of intraoperative effusion: grade 0, no obvious effusion; grade 1, slight effusion and a few intraperitoneal exudation; grade 2, moderate effusion and continuous intraperitoneal exudation necessitating interrupted suction; grade 3, severe effusion and continuous intraperitoneal exudation necessitating constant suction. Four categories of fibrosis: grade 0, no fibrosis; grade 1, slight fibrosis with threadiness fibrous bands, clear dissecting space could be found between the fibrous tissues and adventitia/normal tissues; grade 2, moderate fibrosis with flaky fibrous tissues, the difficulty of tissue and lymph nodes dissection increased although dissecting space could be found between the fibrous tissues and adventitia/normal tissues; grade 3, severe fibrosis with hard and flaky fibrous membrane, the difficulty of tissue and lymph nodes dissection increased extremely and the fibrous tissues merges with adventitia/normal tissues without dissecting space. The relationships of TRG system with tumor response evaluation by computed tomography (CT), tumor regression score, surgical duration, number of retrieved lymph nodes, number of metastatic lymph nodes, number of enlarged lymph nodes seen in the preoperative CT scans as well as postoperative complications were analyzed using t test, χ² test and logistic regression model.

RESULTSNineteen male and 11 female patients with a mean age of(59.1±9.4) years were enrolled. There were 17 cases of grade 1, 12 cases of grade 2 and 1 case of grade 3 for tissue edema, while the corresponding number was 14, 15 and 1 for intraoperative effusion and 15, 14 and 1 for fibrosis respectively. There were no significant differences among the different degrees of tissue edema, intraoperative effusion and fibrosis in terms of the tumor response evaluation by CT and tumor regression score (all P>0.05). The results of logistics regression showed that tumor response evaluation by CT was related with the degree of tissue edema (P=0.012) and intraoperative effusion (P=0.007), rather than the degree of fibrosis (P=0.527). However, tumor regression score was not related with the degree of tissue edema(P=0.345), intraoperative effusion (P=0.159) and fibrosis (P=0.207). Surgical duration of one case with all grade 3 in tissue edema, intraoperative effusion and fibrosis was 408 minutes, which was longer than those with grade 1 and grade 2 patients [(295.9±40.1) minutes and (293.1±34.3) minutes, respectively]; the number of retrieved lymph nodes, metastatic lymph nodes, and enlarged lymph nodes seen in the preoperative CT scans of this case with all grade 3 were 25, 4 and 1, which were all less than those with grade 1 and grade 2 (42.3±11.9 and 38.5±18.2, 7.3±9.1 and 8.1±9.7, 1.8±1.6 and 2.3±1.3, respectively). There were no significant differences between grade 1 and grade 2 of tissue edema, intraoperative effusion and fibrosis in terms of surgical duration, retrieved lymph nodes, metastatic lymph nodes and enlarged lymph nodes seen in the preoperative CT scans(all P>0.05). Four patients suffered from pulmonary complications and 2 patients experienced slight lymphatic, and all leakage were cured by conservative therapies. There were no significant differences among the different grades of tissue edema, intraoperative effusion and fibrosis in terms of the operation-associated complications (all P>0.05).

CONCLUSIONThe tissue response grading system can assist the judgment of operation difficulty and reflect the effectiveness of neoadjuvant chemotherapy to some extent, which has the possibility of applications.

Aged ; China ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Male ; Middle Aged ; Neoadjuvant Therapy ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; surgery

OBJECTIVETo investigate the feasibility and efficacy of clockwise modularized lymphadenectomy in laparoscopic gastrectomy for gastric cancer.

METHODSClinical data of 19 cases who underwent the laparoscopic clockwise modularized lymphadenectomy for gastric cancer (clockwise group) from July 2016 to September 2016 were analyzed retrospectively. The clockwise modularized lymphadenectomy included the fixed operative order, detailed procedure and requirement of lymphadenectomy, which mainly reflected in assisting the exposure of operative field and dissection of lymph nodes through suspending the liver and banding the greater omentum, as well as proposing the requirements and attentions for the dissections of each station of lymph nodes to facilitate the quality control of lymphadenectomy. The operative time, intraoperative complications, intraoperative estimate blood loss, number of total harvested lymph nodes, morbidity and postoperative recovery, were compared with the data of another 19 cases who received traditional lymphadenectomy from January 2016 to June 2016 (control group).

RESULTSThe baseline data were comparable between two groups. All the patients were performed successfully by laparoscopy without conversion and intraoperative complications. The operative time, intraoperative estimated blood loss and number of total harvested lymph node were (278.4±29.9) min, (91.1±41.6) ml and 38.2±15.1 in clockwise group, and were (296.7±30.3) min, (102.2±32.2) ml and 37.0±12.3 in control group without significant differences (all P>0.05). However, the mean number of retrieved No.11p lymph nodes was 2.2±1.8 in clockwise group, which was significantly higher than that in control group (0.8±1.0) (P=0.013). Four patients in each group suffered from pulmonary infections, who were cured by conservative therapies. There was no anastomotic leakage, intraperitoneal hemorrhage, intraperitoneal infection or intestinal obstruction in each group.

CONCLUSIONThe clockwise modularized lymphadenectomy can contribute to the facilitation of the retraction and exposure, decrease of the surgical duration and intraoperative blood loss, and radicalization of lymph node dissection, especially for the lymph nodes dissection around the celiac trunk.

Blood Loss, Surgical ; prevention & control ; statistics & numerical data ; Convalescence ; Gastrectomy ; methods ; Humans ; Intraoperative Complications ; epidemiology ; Laparoscopy ; methods ; Lymph Node Excision ; methods ; statistics & numerical data ; Lymph Nodes ; surgery ; Operative Time ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome

OBJEVTIVETo investigate the expression of cysteine-rich secretory protein 2 (CRISP2) in spermatozoa of patients with asthenozoospermia and explore its clinical significance.

METHOSSemen samples were collected from 24 normal volunteers and 24 patients with asthenozoospermia for detecting CRISP2 mRNA and protein expressions using qRT-PCR and Western blotting, respectively. The correlation of CRISP2 expressions with sperm morphology, progressive motility and fertility prognosis were analyzed in patients with asthenozoospermia.

RESULTSCRISP2 protein expression was obviously lowered in the ejaculated spermatozoa of patients with asthenozoospermia as compared to the normal volunteers, but no significant difference in CRISP2 mRNA expression was found between the two groups. Correlation analysis showed that CRISP2 protein expression was positively correlated with normal sperm morphology (r=0.6182, P=0.0037) and progressive motility (r=0.6309, P=0.0029). Follow-up study of the patients revealed a higher fertility rate in patients with a relatively high CRISP2 protein expression than in those with low CRISP2 protein expression (80.0% vs 20.0%, P=0.0230).

CONCLUSIONThe expression level of CRISP2 protein is positively correlated with normal sperm morphology and progressive motility. A reduced CRISP2 protein expression indicates poor fertility prognosis of patients with asthenozoospermia, suggesting the potential value of CRISP2 as a novel therapeutic target for treating asthenozoospermia.

Asthenozoospermia ; metabolism ; Case-Control Studies ; Fertility ; Follow-Up Studies ; Glycoproteins ; metabolism ; Humans ; Male ; RNA, Messenger ; Sperm Motility ; Spermatozoa ; metabolism

OBJECTIVETo observe the effect of activation of Notch1 signaling pathway by Notch intracellular domain (NICD) plasmid transfection on pancreatic cancer cell proliferation and explore the underlying mechanism.

METHODSThe transfection rates were observed under microscope with fluorescence stimulation, and mRNA expression levels of Hes1 were detected by real-time PCR. Cell proliferation changes were evaluated by CCK-8 after NICD and control plasmid transfection in pancreatic cancer cells. Caspase 3 activity was examined using a caspase 3 detection kit.

RESULTSThe transfection rates of NICD plasmid were up to 80% by fluorescence stimulation observation. Hes1 expression was significantly increased after NICD plasmid transfection, suggesting the activation of Notch1 signaling pathway. NICD plasmid transfection significantly promoted cancer cell proliferation compared to control plasmid transfeciton. The activities of caspase 3 were obviously decreased after NICD plasmid transfection in 3 pancreatic cancer cell lines.

CONCLUSIONActivation of Notch1 signaling pathway by NICD plasmid transfection can promote the proliferation of pancreatic cancer cells by inhibiting the apoptosis pathway.

Apoptosis ; Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Homeodomain Proteins ; metabolism ; Humans ; Pancreatic Neoplasms ; metabolism ; pathology ; Plasmids ; Receptor, Notch1 ; genetics ; metabolism ; Signal Transduction ; Transcription Factor HES-1 ; Transfection

Objective To observe the effect of activation of Notch1 signaling pathway by Notch intracellular domain (NICD) plasmid transfection on pancreatic cancer cell proliferation and explore the underlying mechanism. Methods The transfection rates were observed under microscope with fluorescence stimulation, and mRNA expression levels of Hes1 were detected by real-time PCR. Cell proliferation changes were evaluated by CCK-8 after NICD and control plasmid transfection in pancreatic cancer cells. Caspase 3 activity was examined using a caspase 3 detection kit. Results The transfection rates of NICD plasmid were up to 80% by fluorescence stimulation observation. Hes1 expression was significantly increased after NICD plasmid transfection, suggesting the activation of Notch1 signaling pathway. NICD plasmid transfection significantly promoted cancer cell proliferation compared to control plasmid transfeciton. The activities of caspase 3 were obviously decreased after NICD plasmid transfection in 3 pancreatic cancer cell lines. Conclusions Activation of Notch1 signaling pathway by NICD plasmid transfection can promote the proliferation of pancreatic cancer cells by inhibiting the apoptosis pathway.

Objective To observe the effect of activation of Notch1 signaling pathway by Notch intracellular domain (NICD) plasmid transfection on pancreatic cancer cell proliferation and explore the underlying mechanism. Methods The transfection rates were observed under microscope with fluorescence stimulation, and mRNA expression levels of Hes1 were detected by real-time PCR. Cell proliferation changes were evaluated by CCK-8 after NICD and control plasmid transfection in pancreatic cancer cells. Caspase 3 activity was examined using a caspase 3 detection kit. Results The transfection rates of NICD plasmid were up to 80% by fluorescence stimulation observation. Hes1 expression was significantly increased after NICD plasmid transfection, suggesting the activation of Notch1 signaling pathway. NICD plasmid transfection significantly promoted cancer cell proliferation compared to control plasmid transfeciton. The activities of caspase 3 were obviously decreased after NICD plasmid transfection in 3 pancreatic cancer cell lines. Conclusions Activation of Notch1 signaling pathway by NICD plasmid transfection can promote the proliferation of pancreatic cancer cells by inhibiting the apoptosis pathway.