OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

BACKGROUND: Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China. METHODS: This cross-sectional study enrolled all infants born at 24 +0 to 31 +6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage. RESULTS: A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks' gestation to 3120/3960 (78.8%) at 30 to 31 weeks' gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS. CONCLUSIONS The use rate of ACS remained low for infants at 24 to 31 weeks' gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.
Humans ; Infant, Newborn ; Infant ; Pregnancy ; Female ; Gestational Age ; Infant, Premature ; Intensive Care Units, Neonatal ; Cross-Sectional Studies ; Adrenal Cortex Hormones/therapeutic use*

Objective:Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan.Methods:Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P>0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results:A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 μg/L (OR=5.870, 95% CI: 3.281-10.502, P<0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P<0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P=0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P<0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P<0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P<0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 μg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results ( P=0.415). Conclusion:A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

Objective:Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan.Methods:Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P>0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results:A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 μg/L (OR=5.870, 95% CI: 3.281-10.502, P<0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P<0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P=0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P<0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P<0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P<0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 μg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results ( P=0.415). Conclusion:A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.

Objective: To investigate the effects of two nanotopographies of ultraviolet (UV)-treated titanium surface on macrophage biological behaviour and inflammatory cytokines secretion, and to provide basis for clinical application of UV-treatment in dental implant modification. Methods: Titanium disks were allocated into two groups. Samples in one group were acid-etched in hydrofluoric acid (Acid Ti group), and those in the other group were acid-etched and anodized (Anodization group) to form two nanotopographies respectively. The surface morphology was evaluated by field-emission scanning electron microscopy (FE-SEM). The samples were stored in the dark for 8 weeks. Thirteen samples from each group were exposed to UV-irradiation for 48 h (Acid Ti+UV group and Anodization+UV group), UV-untreated samples from Acid Ti and Anodization groups served as control. Hydrophilicity of samples was measured using contact angle measuring device. After 4, 24 and 72 h of incubation, macrophage cell adhesion and proliferation were conducted using cell counting kit-8. Cytokine/chemokine secretions [tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α)] were measured from cell culture supernatants at 24 and 72 h using magnetic luminex assay. Cell morphology was examined using FE-SEM after 2 h of incubation. Results: Micropitted/nanopillar and micropitted/nanotubular topographies were observed in Acid Ti group and Anodization group respectively. Contact angles in Acid Ti+UV and Anodization+UV groups (20.2°±2.8° and 0.0°±0.0°) were significantly smaller than those in the Acid Ti and Anodization groups (P<0.05). Cell adhesion and proliferation in all groups at 4 and 24 h showed no difference (P>0.05). Cell proliferation in Acid Ti+UV and Anodization+UV groups at 72 h were (0.92±0.13) and (1.10±0.08) respectively, which were significantly higher than those in Acid Ti and Anodization groups. TNF-α concentration in Acid Ti+UV and Anodization+UV groups at 72 h were (1.03±0.11) and (0.87±0.10) ng/L, MCP-1 were (301.7±50.3) and (240.8±18.7) ng/L, MIP-1α were (224.9±30.6) and (233.9±14.9) ng/L respectively, which were significantly lower than those in Acid Ti and Anodization groups (P<0.05). Conclusions UV treatment can increase hydrophilicity of two titanium surface topographies, especially of Anodization+UV group. UV-treated titanium surfaces can promote macrophage proliferation and reduce the inflammatory response in vitro.

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1?Ras, Raf?MEK?ERK, PI3K?AKT?mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD?L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1?Ras, Raf?MEK?ERK, PI3K?AKT?mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD?L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.