BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Abstract To investigate the curative effects of modified submucosal tunnel endoscopic resection(STER) and endoscopic submucosal resection(ESE) in the treatment of paracardial submucosal tumors. Eighty-four patients with paracardial submucosal tumors diagnosed through digestive endoscopy and endoscopic ultrasonography signed informed consent forms, and they were randomly divided into observation group(n=42) and control group(n=42) with the help of the table of random numbers. Patients in the control group received ESE treatment. Patients in the observation group received modified STER surgery.The operation time, average hospitalization time and treatment cost of patients in STER group were(61.32±32.01) min,(8.11±2.42) d and(21.7±3.4) thousand Chinese Yuan respectively, which were better than those in ESE group(87.63±34.09) min,(10.05±2.84) d and(25.9±3.9) thousand Chinese Yuan. The difference was statistically significant(P<0.05). The average number of titanium clips used in the observation group was(5.00±1.37), and in the control group the average number was(4.68±1.25). The difference was not statistically significant. In the STER group, there were 2 cases of intraoperative perforation and 1 case of delayed bleeding. In the ESE group, there were 4 cases of intraoperative perforation and 3 cases of intraoperative uncontrollable bleeding. The incidence of postoperative complications in the STER group was lower than that in the ESE group. The postoperative pathological examination revealed that in both groups the tumors were mostly stromal tumor and leiomyoma. A few of the patients were suffering from lipomas and schwannomas. There was no significant difference in terms of the pathological composition of the patients between the two groups.

BACKGROUND: Fibroblast activation protein (FAP) is one of the surface markers of cancer-associated fibroblasts (CAFs) and is closely related to the malignant characterization of CAFs. SP13786 is a specific micromolecule inhibitor of FAP and this study is to investigate the effects and mechanism of SP13786 on the migration and invasion of A549 cells through regulating exosomes of CAFs. METHODS: CAFs and paracancerous fibroblasts (PTFs) were isolated and subcultured from freshly resected lung adenocarcinoma tissues and paracancerous normal tissues separately. MTT assay was used to detect the proliferation of CAFs incubated by different concentrations of SP13786; PTFs-exo, CAFs-exo and CAFs+SP13786-exo were extracted by polymer precipitation method. The A549 cells were divided into Ctrl group, PTFs group, CAFs group and SP13786 group and each group was incubated with DMEM, PTFs-exo, CAFs-exo and CAFs+SP13786-exo separately. Laser confocal microscope was used to observe the endocytoses of exosomes by A549 cells. The expression of alpha-smooth muscle actin (α-SMA) and FAP in PTFs and CAFs and the expression of E-cadherin, N-cadherin, Slug, Stat3 and P-Stat3 in A549 cells were detected by immunofluorescence, immunohistochemistry and Western blot. The migration and invasion ability of A549 cells were detected by cell scratch and transwell methods. RESULTS: α-SMA and FAP were expressed much higher in CAFs than that in PTFs which indicate that CAFs and PTFs were successfully obtained from lung adenocarcinoma and paracancerous tissues (P<0.05). MTT showed that the 50% inhibitory concentration (IC50) of SP13786 for CAFs was about 3.3 nmol/L. In addition, SP13786 can significantly decrease the expression of α-SMA and FAP in CAFs which means that targeted inhibition of FAP could reduce the malignant characteristics of CAFs (P<0.05). Laser confocal microscope found that exosomes from CAFs could be taken up by A549 cells and scratch and transwell tests showed that the endocytosed CAFs-exo could promote the migration and invasion of A549 cells (P<0.001), while FAP inhibitor SP13786 could inhibit the effects of CAFs-exo on A549 cells (P<0.05). Furthermore, Immunofluorescence and Western blot showed that CAFs-exo could promote EMT by decreasing E-cadherin expression and increasing N-cadherin, Slug expression in A549 cells while FAP inhibitor SP13786 could significantly supress CAFs-exo-induced epithelial-mesenchymal transition (EMT) of A549 cells (P<0.05). Moreover, the expression of P-Stat3 was obviously increased in A549 cells of CAFs group and significantly down-regulated in SP13786 group (P<0.05) whereas there was no significant difference in total Stat3 between CAFs and SP13786 groups (P>0.05). Finally, WP1066 (a specific inhibitor of Stat3) was used to comfirm whether SP13786 could influence EMT of A549 cells by inhibiting Stat3 phosphorylation via CAFs-Exo. The results showed that when the phosphorylation of Stat3 in CAFs group was inhibited by WP1066, SP13786 could not influence the P-Stat3 expression and EMT of A549 cells anymore (P>0.05). CONCLUSIONS As a specific micromolecule inhibitor of FAP, SP13786 indirectly inhibits the migration and invasion of A549 cells by affecting exosomes of CAFs. The possible mechanism is to inhibit the phosphorylation of Stat3 and thus affect the EMT of A549 cells.

OBJECTIVE: To explore the genetic basis for a case of Lamb-Shaffer syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing. RESULTS: The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
Animals ; Genomics ; Heterozygote ; Humans ; Mutation ; SOXD Transcription Factors/genetics* ; Sheep ; Whole Exome Sequencing

BACKGROUND: ANXA2 plays a very important role in cancer progression. chemokine ligand 18 (CCL18) is associated with the invasion, migration, metastasis and poor prognosis of lung adenocarcinoma (LUAD). In this study, we aimed to explore whether CCL18 promotes LUAD invasion through ANXA2, and its role and molecular mechanism in LUAD invasion. METHODS: Western blot was used to detect ANXA2 expression in LUAD tissues and adjacent non-tumor tissues, the transfection efficiency of SiANXA2#2 in cells and the role of ANXA2 as an upstream regulator in the AKT/cofilin signaling pathway. In vitro cytological experiments such as chemotaxis experiment and transwell invasion test was used to explore the mechanism of ANXA2 on LUAD metastasis. F-actin polymerization experiment and Western blot were used to detect whether invasion ability alteration of SiANXA2#2 A549 cells are related to F-actin. RESULTS: Western blot analysis showed that compared with adjacent non-tumor tissues, the protein expression level of ANXA2 in cancer tissues increased (P<0.05). In the chemotaxis experiment and invasion experiment, the chemotaxis and invasion ability induced by CCL18 decreased when ANXA2 knockdowned (P<0.05). Compared with the control group, F-actin polymerization was significantly lower in ANXA2 knockdown group, while phosphorylation of AKT at Ser473 and Thr308 and phosphorylation of Cofilin and LIMK were reduced in ANXA2 knockdown group (P<0.05). CONCLUSIONS ANXA2 knockdown can reduce the invasive effect of CCL18 on LUAD cells by reducing phosphorylation of AKT and downstream pathways.

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

Objective:To explore the feasibility of fast and accurate osteotomy using a new angle adjustable osteotomy guide (AAOG) in closing wedge distal femoral osteotomy(CWDFO).Methods:The clinical data of 14 patients (17 knees) with valgus knee treated with CWDFO at Department of Integrated Chinese and Western Medicine Orthopedics, Honghui Hospital, Xi′an Jiaotong University from January 2018 to July 2019 were analyzed retrospectively. There were 3 males and 11 females, aging (41.4±16.4) years (range: 18 to 56 years). The body mass index was (23.5±3.5) kg/m 2 (range: 18.1 to 28.9 kg/m 2). The guide pins were placed with the assistance of the self-designed AAOG. Before the surgery, Solidworks software was used to calculate the correction angle and the osteotomy radius accurately. The osteotomy guide was adjusted according to these two parameters. During the surgery, the adjusted osteotomy guide was placed to the surface of bone closely and the guide pins were drilled into the bone through the guide holes. The position of the guide pins was confirmed under fluoroscopy. The osteotomy was finished under guide of pins and fixed with Tomofix plate (Synthes). The times and duration of placement of the guide pins, the times of X-ray examination, the planned and actual thickness of the osteotomy wedge, the top and bottom area of the osteotomy wedge, the posterior distal femoral angle(PDFA), the correction of the weight line, and the American Knee Society Score(AKSS) and Tegner scores were collected and compared by paired t test or Kruskal-Wallis non-parametric test. Healing time after osteotomy and complications were recorded. Results:The guide pins were successfully placed once in 10 knees, adjusted once in 5 knees and twice in 2 knees. The time spent in placing all the 6 pins was 82.4 seconds (range: 51 to 125 seconds), and the times of X-ray examination was 1.5 times (range: 1 to 5 times). The top and bottom areas of the osteotomy wedge were (5.52±0.52)cm 2 and (5.36±0.49)cm 2. PDFA was (85.2±2.6)° preoperatively and (85.5±1.4)° postoperatively ( t=-0.401, P>0.05). The thickness of the osteotomy was (11.3±1.9)mm according to the preoperative plan, and the actual thickness was (8.1±1.7)mm. All the patients were followed up for 6 months after surgery and AKSS and Tegner scores improved significantly (all P<0.05). The correction of the weight lines was within the ideal range. Fractures of the hinge point occurred in 3 knees. All of the osseous healing without complications. Conclusion:The new osteotomy guide helps to place the guide pins rapidly and precisely according to the preoperative planning, which should be widely used in clinical applications with promising outcomes.

Objective:To explore the feasibility of fast and accurate osteotomy using a new angle adjustable osteotomy guide (AAOG) in closing wedge distal femoral osteotomy(CWDFO).Methods:The clinical data of 14 patients (17 knees) with valgus knee treated with CWDFO at Department of Integrated Chinese and Western Medicine Orthopedics, Honghui Hospital, Xi′an Jiaotong University from January 2018 to July 2019 were analyzed retrospectively. There were 3 males and 11 females, aging (41.4±16.4) years (range: 18 to 56 years). The body mass index was (23.5±3.5) kg/m 2 (range: 18.1 to 28.9 kg/m 2). The guide pins were placed with the assistance of the self-designed AAOG. Before the surgery, Solidworks software was used to calculate the correction angle and the osteotomy radius accurately. The osteotomy guide was adjusted according to these two parameters. During the surgery, the adjusted osteotomy guide was placed to the surface of bone closely and the guide pins were drilled into the bone through the guide holes. The position of the guide pins was confirmed under fluoroscopy. The osteotomy was finished under guide of pins and fixed with Tomofix plate (Synthes). The times and duration of placement of the guide pins, the times of X-ray examination, the planned and actual thickness of the osteotomy wedge, the top and bottom area of the osteotomy wedge, the posterior distal femoral angle(PDFA), the correction of the weight line, and the American Knee Society Score(AKSS) and Tegner scores were collected and compared by paired t test or Kruskal-Wallis non-parametric test. Healing time after osteotomy and complications were recorded. Results:The guide pins were successfully placed once in 10 knees, adjusted once in 5 knees and twice in 2 knees. The time spent in placing all the 6 pins was 82.4 seconds (range: 51 to 125 seconds), and the times of X-ray examination was 1.5 times (range: 1 to 5 times). The top and bottom areas of the osteotomy wedge were (5.52±0.52)cm 2 and (5.36±0.49)cm 2. PDFA was (85.2±2.6)° preoperatively and (85.5±1.4)° postoperatively ( t=-0.401, P>0.05). The thickness of the osteotomy was (11.3±1.9)mm according to the preoperative plan, and the actual thickness was (8.1±1.7)mm. All the patients were followed up for 6 months after surgery and AKSS and Tegner scores improved significantly (all P<0.05). The correction of the weight lines was within the ideal range. Fractures of the hinge point occurred in 3 knees. All of the osseous healing without complications. Conclusion:The new osteotomy guide helps to place the guide pins rapidly and precisely according to the preoperative planning, which should be widely used in clinical applications with promising outcomes.

Objective To evaluate the biomechanical effects of lateral meniscus posterior root (LMPR) tears fixed at different suture positions, so as to investigate the optimal suture method for repairing LMPR tears. Methods Eight fresh cadaveric knees were used. Each knee was tested under 6 conditions: intact knee, ruptur of LMPR, suture of LMPR to the center point of root insertion, suture of LMPR posterior, interior and later 5 mm to the center point of root insertion, respectively. The peak contact pressure, the average contact pressure and contact area were evaluated using a Tek-scan sensor positioned between the meniscus and tibial plateau, under 1 kN compressive loading, at 0 degree knee extension. Results In the lateral compartment, the average contact pressure and peak pressure significantly increased under rupture of LMPR compared with the intact state (P<0.01), and the contact area decreased significantly (P<0.05). For LMPR tears fixed by four different suture methods, both the average pressure and peak contact pressure reduced, and the contact area increased. The average contact pressure, peak pressure and contact area were closer to the knee joint in the intact state when the suture positions of LMPR tears was posterior 5 mm to the center point of root insertion (P<0.05). In the medial compartment, there were no significant differences in contact pressure, peak contact pressure and contact area with the knee joint at 0 degree (P>0.05). Conclusions The average contact pressure, the peak contact pressure and the contact area between the lateral meniscus and the tibial plateau changed obviously due to the LMPR tears. When the suture position was 5 mm lateral to the center point of root insertion, similar biomechanical function with the intact knee could be obtained.

PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRI was determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.
Alanine Transaminase ; Aspartate Aminotransferases* ; Aspartic Acid* ; Biomarkers ; Blood Platelets ; Carcinoembryonic Antigen ; Cholangiocarcinoma* ; Disease-Free Survival ; Hepatectomy* ; Hepatitis B ; Humans ; Leukocytes ; Lymph Nodes ; Lymphocytes ; Multivariate Analysis ; Neoplasm Metastasis ; Neutrophils* ; Prognosis* ; Recurrence ; Retrospective Studies ; ROC Curve