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

OBJECTIVES: To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC. METHODS: A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model. RESULTS: The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value. CONCLUSIONS Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.
Asphyxia/complications* ; Child ; Enterocolitis, Necrotizing/etiology* ; Female ; Fetal Growth Retardation ; Humans ; Hypoalbuminemia ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases/etiology* ; Nomograms ; Sepsis/complications*

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

Advanced non-small cell lung cancer is one of the most difficult malignant tumors in the world. At present, chemotherapy is the most common treatment for NSCLC. However, traditional chemotherapy can kill tumor cells as well as normal cells. In order to solve this problem, metronomic chemotherapy came into being. It can inhibit tumor angiogenesis and tumor growth through a continuous high-frequency, low-dose administration. Metronomic chemotherapy can effectively control the disease progression of advanced NSCLC patients, delay their life span and improve their quality of life. Therefore, metronomic chemotherapy has become an effective treatment for advanced non-small cell lung cancer.

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 Lung cancer is one of the most common types of malignancy, and the incidence and mortality are the highest among cancers. Increasing the diagnostic rate of early-stage lung cancer is very important to improve the prognosis of patients. The occurrence and development of lung cancer is a complex process mediated by multiple genes and multiple signaling pathways. The detection of biomarkers has received great attention in the early diagnosis of lung cancer. With the deepening of research and advances in detection technology, biomarkers such as autoantibodies, exosomes, circulating tumor cells, circulating tumor DNA, and DNA methylation of lung cancer have been continuously discovered, and precision medicine has been deeply rooted in the hearts of people. This article gives an overview of the research progress of biomarkers in the early diagnosis of lung cancer.

Objective To investigate the application of diffusion tensor imaging (DTI) in evaluating prognosis of patients with moderate and severe diffuse axonal injury (DAI).Methods A prospective cohort study was made on 35 patients with moderate and severe DAI,who were enrolled from June 2013 to December 2015 as study group.There were 21 males and 14 females,with age of (55.1 ± 11.6) years.The Glasgow coma scale (GCS) was (8.2 ± 2.9)points on admission.Moderate DAI was seen in 20 patients and severe DAI in 15 patients.Other 15 healthy volunteers were selected as control group.Fractional anisotropy (FA) was measured by DTI in three areas of interests as follows:the corpus callosum,thalamus,and brainstem areas.Glasgow outcome scale (GOS) was adopted to assess the prognosis of DAI patients at 6 months after the injury.The FA values of the three areas between study group and control group as well as FA values of patients when they were admitted to hospital and 6 months after injury were measured.In this way,the relationship between the FA values of different areas of interests in DAI patients on admission and the prognosis 6 months after injury was analyzed.Results The FA values of the corpus callosum,thalamus and brainstem area in study group were all lower than those in control group (P ＜ 0.05).Further,FA values of the corpus callosum,thalamus,brainstem area in severe DAI patients were lower than those of moderate DAI patients (P ＜ 0.05).FA values of the corpus callosum,thalamus,brain stem areas in DAI patients at 6 months after injury were lower than those of corresponding areas when DAI patients were admitted to hospital (P ＜ 0.05).FA values of the corpus callosum,thalamus and brain stem on admission were significantly positively correlated with GOS at 6 months after injury (P ＜ O.05).Conclusions Lower FA values of the corpus callosum,thalamus and brainstem area in patients with moderate and severe DAI are associated with more severe injury and worse prognosis.DTI scans can be used as a valuable tool to evaluate the prognosis of DAI patients.

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

Bone morphogenetic protein-4(BMP4) is one of BMPs member,it not only can play an important role in cell proliferation and invasion,but also play an important role in cell differentiation,apoptosis and angiogenesis.A study showed BMP4 in malignant tumor can inhibit the growth of tumor cells,and also can induce tumor cell invasion,metastasis and epithelial mesenchymal transformation,and SMAD is the classic signaling pathways.BMP4 is expected to become a potential therapeutic targets and in evaluating the prognosis,immune therapy in malignant tumor.In this paper,the structure and function of BMP4 and its mechanism in tumor were reviewed.