Immunogenic hypofractionated radiotherapy sensitising head and neck squamous cell carcinoma to anti-PD-L1 therapy in MDSC-dependent manner.

BACKGROUND: Enhancing the response rate of immunotherapy will aid in the success of cancer treatment. Here, we aimed to explore the combined effect of immunogenic radiotherapy with anti-PD-L1 treatment in immunotherapy-resistant HNSCC mouse models. METHODS: The SCC7 and 4MOSC2 cell lines were irradiated in vitro. SCC7-bearing mice were treated with hypofractionated or single-dose radiotherapy followed by anti-PD-L1 therapy. The myeloid-derived suppressive cells (MDSCs) were depleted using an anti-Gr-1 antibody. Human samples were collected to evaluate the immune cell populations and ICD markers. RESULTS: Irradiation increased the release of immunogenic cell death (ICD) markers (calreticulin, HMGB1 and ATP) in SCC7 and 4MOSC2 in a dose-dependent manner. The supernatant from irradiated cells upregulated the expression of PD-L1 in MDSCs. Mice treated with hypofractionated but not single-dose radiotherapy were resistant to tumour rechallenge by triggering ICD, when combined with anti-PD-L1 treatment. The therapeutic efficacy of combination treatment partially relies on MDSCs. The high expression of ICD markers was associated with activation of adaptive immune responses and a positive prognosis in HNSCC patients. CONCLUSION: These results present a translatable method to substantially improve the antitumor immune response by combining PD-L1 blockade with immunogenic hypofractionated radiotherapy in HNSCC.

Buchwald-Hartwig amination of aryl esters and chlorides catalyzed by the dianisole-decorated Pd-NHC complex.

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

[Clinical characteristics and genetic analysis of a pedigree affected with neonatal central core disease].

OBJECTIVE: To investigate the possible causative factors of central core disease(CCD), the clinical features of a neonatal case with CCD and five patients in the pedigree line were analyzed for RYR1 gene variant. METHODS: Medical and family history inquiries and detailed clinical examinations were performed in the proband. High-throughput sequencing technology was applied to analyze the gene variant of the proband, and Sanger sequencing was applied to verify the pedigree distribution of the variant. RESULTS: The whole exon sequencing results showed that the proband has a missense variant of c. 14591A>C (p.Tyr4864Ser) in the RYR1 gene which was unreported previously; Sanger sequencing results showed that the father, grandfather, the eldest aunt and second aunt of the proband all carried the same variant. The c.14591 A>C variant of RYR1 gene was predicted to be a likely pathogenic (PM2+PM5+PP1+PP3) according to the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION: The RYR1 gene c.14591A>C (p.Tyr4864Ser) variant may be the genetic cause of the pedigree and genetic testing helps to clarify the diagnosis. Identification of this variant has enriched the variant spectrum of the RYR1 gene.

Overexpression of RRM2 is related to poor prognosis in oral squamous cell carcinoma.

OBJECTIVES: Ribonucleotide reductase M2 (RRM2) is a rate-limiting enzyme involved in DNA repair and synthesis. This study aimed to investigate the expression level, clinicopathological significance, and prognostic value of RRM2 in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Human OSCC tissue microarrays were used to detect the expression of RRM2, cancer stem cell (CSC) markers CD44 and aldehyde dehydrogenase 1 (ALDH1), and the epithelial-mesenchymal transition (EMT) marker Slug. The correlation of RRM2 expression with clinicopathological parameters was evaluated. The effects of RRM2 on cell proliferation, migration, and apoptosis were investigated. RESULTS: Compared with normal and dysplastic tissues, the expression of RRM2 in human primary OSCC was significantly increased, and its overexpression was correlated with advanced pathological grade. The overall survival rate of patients with high RRM2 expression was lower than that of patients with low RRM2 expression. The overexpression of RRM2 was significantly associated with OSCC recurrence, and its overexpression was correlated with the CSC markers CD44 and ALDH1 and the EMT marker Slug. The expression of RRM2 promotes the proliferation and migration of human OSCC cells and inhibits apoptosis. CONCLUSION: Ribonucleotide reductase M2 may be a novel target in the diagnosis, prognosis, and therapy of OSCC.

[Clinical characteristics and molecular genetics of seven neonates with congenital nephrogenic diabetes insipidus].

OBJECTIVE: To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results. RESULTS: The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found to harbor pathogenic variants of the AVPR2/AQP2 gene, which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC, two missense mutations of c.541C>T and c.419C>A, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 and 7 were a pair of twins. Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene, which was known to be pathogenic. CONCLUSION: AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants.

BACKGROUND: Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants. METHODS: A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks. RESULTS: The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96-1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28-296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000-1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment. CONCLUSIONS: Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073 ; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500 .

Overexpression of ATAD2 indicates Poor Prognosis in Oral Squamous Cell Carcinoma.

ATPase family AAA domain-containing protein 2 (ATAD2) is highly expressed in a variety of malignancies and can promote the proliferation of tumor cells and inhibit their differentiation. However, the expression of ATAD2 and its related mechanism in oral squamous cell carcinoma (OSCC) are still unknown. Immunohistochemical staining of ATAD2, cancer stem cells (CSCs) markers and immune checkpoint molecules was conducted on human OSCC specimens to determine the expression levels of these proteins and their correlations with the clinicopathological characteristics of ATAD2 in OSCC. Moreover, the role of ATAD2 in cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT) were assessed by silencing ATAD2 in vitro. Immunohistochemical analysis revealed that ATAD2 expression in OSCC tissues was markedly higher than that in adjacent dysplastic tissues and normal mucosal tissues. Overexpression of ATAD2 was related to poor overall survival in OSCC patients. In addition, the protein expression of ATAD2 was notably correlated with the expression of B7-H4, PD-L1, CMTM6, Slug and ALDH1 in human OSCC. ATAD2 knockdown arrested the cell cycle, promoted the apoptosis, and inhibited the proliferation, migration, and EMT of OSCC cells. In conclusion, these findings revealed that ATAD2 is highly expressed in OSCC and can act as a poor prognostic indicator.

Retracted: EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome through negative regulation of mitogen-activated protein kinase axis.

The transcription factor, early B cell factor 1 (EBF1), plays a vital role in the lineage specification involving early B cell development and the onset of myelodysplastic syndrome (MDS). Therefore, to investigate whether or not EBF1 affects MDS as well as the transcription factor's underlying mechanism, we used CD34+ hematopoietic stem cells in bone marrow from patients with MDS. The extracted cells were then transfected with a series of EBF1, short hairpin RNA against EBF1 (shEBF1), and SB203580 (a specific mitogen-activated protein kinase [MAPK] axis inhibitor). The effects EBF1 gene and MAPK axis had on cell proliferation, apoptosis, and migration were determined by in vitro cell culturing. We made observations that involved EBF1 inhibiting the messenger RNA (mRNA) level of p38 MAPK, increasing the mRNA levels of extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase 5 (ERK5), decreasing the protein expression of Bcl-2-associated X protein (Bax), and finally elevating the protein levels of B cell lymphoma/leukemia-2 (Bcl-2), stem cell factor (SCF), erythropoietin receptor (EpoR), p-ERK, p-JNK, p-ERK5, cyclin D, cyclin E, cyclin-dependent kinase 2 (CDK2), and CDK6, implying that EBF1 may very well have an inhibitory role in the MAPK axis. Another discovery found that EBF1 had a positive effect on the promotion of bone marrow CD34+ cell proliferation as well as its migration, but inhibited the apoptosis of cells. The results we obtained from this study indicated that the EBF1 gene suppresses the activation of the MAPK axis, thereby promoting both the proliferation and migration of bone marrow CD34+ cells as well as inhibiting the associating apoptosis. The effects of the EBF1 gene are likely to present a new therapeutic target in preventing the progression of MDS.

Endovascular Treatment of Iliac Artery Stenosis Caused by Takayasu Arteritis: A 10-Year Experience.

Purpose: To evaluate the safety and efficacy of endovascular treatment for iliac artery stenosis caused by Takayasu arteritis (TA). Methods: Twenty-three consecutive TA patients (mean age 28.6±9.5 years; 17 women) with 30 iliac artery stenoses underwent percutaneous transluminal angioplasty (PTA) and selective stent implantation between January 2007 and December 2016. All had claudication (Rutherford category 2 or 3). The changes in the Rutherford category, ankle-brachial index (ABI), 6-minute walking capacity, and adverse events were assessed. Results: The success rate of endovascular therapy for iliac artery lesions was 93.3% (28/30). Guidewires could not cross either lesion in a patient with bilateral stenoses. Twenty-four lesions were treated by PTA alone and the other 4 lesions with provisional stents. One patient had a puncture site hematoma. Over an average of 4.8±3.3 years, 18 patients remained asymptomatic or had mild intermittent claudication. The other 4 patients developed moderate to severe intermittent claudication due to progression of a previously existing iliac lesion (n=1) or restenosis (n=3); all 4 underwent PTA. At the last follow-up, improvements were seen in the ABI (0.95±0.12 vs 0.51±0.22, p<0.001), 6-minute walking capacity (409.5±46.1 vs 272.6±32.3 m, p<0.001), and the Rutherford category of 22 patients. One patient died of a hemorrhagic stroke at 27 months due to uncontrolled hypertension. Conclusion: Endovascular therapy was safe and effective in treating TA patients with iliac artery stenosis, with good clinical outcomes in the long term.

LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the bortezomib sensitivity.

Chromosome 17p deletions (del(17p)) are present in about 11% of newly diagnosed multiple myeloma (MM) patients and related to inferior prognosis. Bortezomib (BTZ), the first proteasome inhibitor anticancer drug, has a good therapeutic effect for newly diagnosed, relapsed or refractory MM, but is unable to improve the outcome of MM patients with del(17p). Long noncoding RNA (lncRNA) PRAL is located on chromosome 17p, and is associated with the progression and prognosis of different types of cancers. However, little is known about its role in MM. Here, we found that PRAL was downregulated in primary MM cells and cell lines, especially in MM cells with del(17p), and was associated with ISS (international staging system) stage and Durie-Salmon stage in MM patients. Survival curves showed that MM patients with low PRAL expression had a significantly shorter disease-free survival (DFS) and overall survival (OS) than the patients with high PRAL expression. Multivariate Cox regression analysis showed that PRAL expression was an independent predictor for DFS and OS. Then cell proliferation, viability, Ki67 expression, and caspase-3 activity detection showed that PRAL promoted MM cell growth inhibition and apoptosis, and potentiated the anti-MM effect of BTZ in vitro. We further identified and confirmed that miR-210 was the target of PRAL, and miR-210 overexpression overturned the potentiation effect of PRAL on BTZ efficacy. Subsequently, bone morphogenetic protein 2 (BMP2) was confirmed to be the target of miR-210, and PRAL positively regulated the derepression of BMP2 by sponging miR-210. Overexpression of BMP2 potentiated the anti-MM effect of BTZ in vitro. In addition, animal experiments further confirmed that PRAL potentiated BTZ efficacy in vivo. Collectively, our study first revealed a critical role of PRAL-miR-210-BMP2 axis in MM progression, prognosis and treatment with BTZ, and PRAL could become a novel diagnostic, prognostic and therapeutic candidate for MM patients especially for the MM patients harboring del(17p) in the future.

Clinical outcomes and influencing factors of in-stent restenosis after stenting for symptomatic stenosis of the vertebral V1 segment.

OBJECTIVE: The objective of this study was to evaluate 30-day and long-term clinical outcomes and influencing factors of in-stent restenosis (ISR) after stenting for symptomatic stenosis of the vertebral V1 segment. METHODS: The clinical and follow-up data of 301 consecutive patients (mean age, 64 ± 8 years; 252 men) with symptomatic V1 stenosis who underwent stenting at the Fuwai Hospital between January 2010 and June 2016 were collected retrospectively. The 30-day and long-term follow-up of stroke and death after stenting and the recurrence of symptoms, ISR, and repeated revascularization were assessed. RESULTS: Technical success was 100%. The mean stenosis of lesions was reduced from 82.8% ± 7.6% to 4.4% ± 4.0% immediately after 312 stents (165 bare-metal stents [BMSs] and 147 drug-eluting stents) were implanted. The overall risk of combined any stroke and death was 1.0% (3/301) within 30 days after stenting. The rates of freedom from any stroke and death were 98.2%, 96.8%, and 91.4% at 1 year, 3 years, and 5 years, respectively. After a mean follow-up of 2.9 ± 1.5 years, 46 (15.8%) patients developed ISR, of whom 19 (6.5%) were symptomatic. Twenty-two (7.6%) patients with ISR underwent repeated revascularization. The primary and assisted patency rates were 90.0% and 95.4%, 82.6% and 90.3%, and 80.3% and 87.9% at 1 year, 3 years, and 5 years, respectively. BMS (hazard ratio, 2.02; 95% confidence interval, 1.01-4.06; P < .05) and diabetes (hazard ratio, 1.87; 95% confidence interval, 1.04-3.37; P = .04) were independently associated with an increased risk of ISR. CONCLUSIONS: Percutaneous stent placement for symptomatic V1 stenosis is safe and associated with a good long-term patency rate. BMS and diabetes are independent predictive factors of ISR.

Thromboxane A2 Receptor Inhibition Suppresses Multiple Myeloma Cell Proliferation by Inducing p38/c-Jun N-terminal Kinase (JNK) Mitogen-activated Protein Kinase (MAPK)-mediated G2/M Progression Delay and Cell Apoptosis.

Multiple myeloma (MM) is a plasma cell malignancy without effective therapeutics. Thromboxane A2 (TxA2)/TxA2 receptor (T prostanoid receptor (TP)) modulates the progression of some carcinomas; however, its effects on MM cell proliferation remain unclear. In this study, we evaluated cyclooxygenase (COX) enzymes and downstream prostaglandin profiles in human myeloma cell lines RPMI-8226 and U-266 and analyzed the effects of COX-1/-2 inhibitors SC-560 and NS-398 on MM cell proliferation. Our observations implicate COX-2 as being involved in modulating cell proliferation. We further incubated MM cells with prostaglandin receptor antagonists or agonists and found that only the TP antagonist, SQ29548, suppressed MM cell proliferation. TP silencing and the TP agonist, U46619, further confirmed this finding. Moreover, SQ29548 and TP silencing promoted MM cell G2/M phase delay accompanied by reducing cyclin B1/cyclin-dependent kinase-1 (CDK1) mRNA and protein expression. Notably, cyclin B1 overexpression rescued MM cells from G2/M arrest. We also found that the TP agonist activated JNK and p38 MAPK phosphorylation, and inhibitors of JNK and p38 MAPK depressed U46619-induced proliferation and cyclin B1/CDK1 protein expression. In addition, SQ29548 and TP silencing led to the MM cell apoptotic rate increasing with improving caspase 3 activity. The knockdown of caspase 3 reversed the apoptotic rate. Taken together, our results suggest that TxA2/TP promotes MM cell proliferation by reducing cell delay at G2/M phase via elevating p38 MAPK/JNK-mediated cyclin B1/CDK1 expression and hindering cell apoptosis. The TP inhibitor has potential as a novel agent to target kinase cascades for MM therapy.

[Expressions of ODF2 mRNA and protein are down-regulated in the sperm of asthenospermia patients].

OBJECTIVE: To investigate the mRNA and protein expressions of outer dense fiber 2 (ODF2) in the sperm of the asthenospermia patient and their differences from those in normal healthy men. METHODS: According to the WHO criteria, we collected semen samples from 45 asthenozoospermia patients and 15 normal healthy volunteers. Using computer-assisted sperm analysis (CASA), we divided the semen samples from the asthenospermia patients into a mild, a moderate and a severe group, and determined the mRNA and protein expressions of ODF2 in different groups by RT-PCR and Western blot. RESULTS: Compared with the normal healthy men, the expression of the ODF2 gene showed no statistically significant difference in the mild asthenospermia group (1.112 0 ± 0.525 5 vs 0.688 0 ± 0.372 0, P >0.05) but remarkably decreased in the moderate (0.483 3 ± 0.186 3, P <0.05) and severe asthenospermia patients (0.448 3 ± 0.340 8, P <0.01). The OD value (ODF2/ß-actin) of the ODF2 protein in the normal men exhibited no statistically significant difference from that in the mild asthenospermia group (0.458 7 ± 0.052 1 vs 0.326 1 ± 0.071 4, P >0.05), but markedly lower than in the moderate (0.145 4 ± 0.053 6, P <0.05) and severe asthenospermia patients (0.122 7 ± 0.045 7, P <0.01), which was consistent with the results of RT-PCR. CONCLUSIONS: Decreased mRNA and protein expressions of ODF2 in the sperm are positively correlated with declined sperm motility of the asthenospermia patient, which is suggestive of the involvement of the ODF2 gene in the regulation of sperm motility.

[Efficacy of heated humidified high-flow nasal cannula in preterm infants aged less than 32 weeks after ventilator weaning].

OBJECTIVE: To investigate the efficacy of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (nCPAP) in preterm infants aged 26-31(+6) weeks with respiratory distress syndrome after ventilator weaning. METHODS: A total of 161 preterm infants were randomly divided into two groups after ventilator weaning: HHHFNC treatment (n=79) and nCPAP treatment (n=82). The two groups were subdivided into 26-28(+6) weeks and 29-31+6 weeks groups according to the gestational age. The treatment failure rate, reintubation rate within 7 days after extubation, incidence of complications, and mortality during hospitalization were compared between the two groups. RESULTS: The treatment failure rate and reintubation rate showed no significant differences between the HHHFNC and nCPAP groups. The preterm infants aged 26-28(+6) weeks in the HHHFNC group had a significantly higher treatment failure rate than those in the nCPAP group (P<0.05), while the reintubation rate showed no significant difference. As for the preterm infants aged 29-31(+6) weeks, the treatment failure rate and reintubation rate showed no significant differences between the two groups. The incidence of complications and mortality showed no significant differences between the HHHFNC and nCPAP groups. CONCLUSIONS: In preterm infants aged 29-31(+6) weeks, HHHFNC has a similar efficacy as nCPAP after ventilator weaning, while in those aged less than 29 weeks, HHHFNC should be used with great caution if selected as the first-line noninvasive respiratory support.

CT Signs Can Predict Treatment Response and Long-Term Survival: A Study in Locally Advanced Esophageal Cancer with Preoperative Chemotherapy.

BACKGROUND: Accurate prediction of treatment response and prognosis before surgery allows prompt therapy adjustment. This study aimed to evaluate the efficacy of computed tomography (CT) signs in predicting treatment response and survival for advanced esophageal squamous cell carcinoma patients who received preoperative chemotherapy. METHODS: This study retrospectively enrolled 135 consecutive patients with preoperative chemotherapy from September 2005 to December 2011. A logistic regression model was used to evaluate the association between pathologic response and CT signs. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and a Cox proportional hazards model was constructed to determine associations between CT signs after neoadjuvant chemotherapy and survival outcomes. RESULTS: Logistic regression showed that the significant predictors of a poor response were the total number of lymph nodes (LNs) (>6) at baseline [odds ratio (OR) 5.07; 95 % confidence interval (CI) 1.86-13.81; P = 0.002] and the CT value change rate (≤17 %) (OR 2.35; 95 % CI 1.05-5.23; P = 0.037). In the Cox analyses, the significant predictors of OS were preoperative tumor thickness (>10 mm) [hazard ratio (HR) 2.33; 95 % CI 1.36-4; P = 0.002), total number of LNs (>6) (HR 1.88; 95 % CI 1.12-3.17; P = 0.017), and short diameter of the largest LN (>10 mm) (HR 1.87; 95 % CI 1.07-3.28; P = 0.028), whereas only the short diameter of the largest LN was a significant predictor of DFS (HR 2.36; 95 % CI 1.23-4.54; P = 0.01). CONCLUSIONS: CT signs can predict therapeutic efficacy and survival outcomes and provide an opportunity to offer additional treatment options before surgery.

Prognosis of very preterm infants with severe respiratory distress syndrome receiving mechanical ventilation.

OBJECTIVE: To evaluate the prognosis of very preterm infants with severe respiratory distress syndrome (RDS) receiving mechanical ventilation. METHODS: A total of 288 preterm infants mechanically ventilated for severe RDS and completed follow-up till 18 months of corrected age comprised these study subjects. The associations of prenatal and postnatal factors, mode and duration of conventional mechanical ventilation (CMV), medication and treatment, and complications with cerebral palsy or mental developmental index (MDI) < 70 at 18 months of age were analyzed. RESULTS: The incidences of CP among study subjects were 17, 5, and 2% in infants less than 28, 28-30, and 30-32 weeks, respectively. The incidences of MDI < 70 were 49, 24, and 13% in infants less than 28 weeks, 28-30 weeks, and 30-32 weeks, respectively. Antenatal corticosteroids, preeclampsia, fetal distress, early and late bacteremia, and decreased weight gain were associated with CP and an MDI < 70. In the CP and MDI < 70 groups, the number of infants on CMV was significantly higher than on high-frequency oscillatory ventilation (HFOV). Longer duration of mechanical ventilation and blood transfusions were associated with an increased risk of having an MDI < 70 or CP. The complications in study subjects associated with an MDI < 70 or CP were BPD, NEC, and IVH grade III-IV. CONCLUSION: The prognosis of very preterm infants with severe RDS may be influenced by several prenatal and postnatal factors. HFOV although decreased the duration of mechanical ventilation, whether it will decrease the incidence of neurodevelopmental disability, needs to be explored further.

The survival predictive significance of HOXC6 and HOXC8 in esophageal squamous cell carcinoma.

BACKGROUND & AIM: Esophageal squamous cell carcinoma (ESCC), a common disease in China, is mainly treated surgically. We established a prospective database of patients with esophageal cancer between January 2000 and December 2010, including 486 subjects with ESCC who underwent surgical treatment. In this study, we explored the prognostic significance of the expressions of HOXC6 and HOXC8, responsible for embryonic development, by studying the specimens collected from clinical subjects during strict follow-up periods. MATERIALS & METHODS: Immunohistochemistry was used to detect the expressions of HOXC6 and HOXC8 in 274 ESCC subjects including 138 ESCC subjects treated with surgery alone and 136 ESCC subjects treated with neoadjuvant chemotherapy. Survival analysis was performed from the day of surgery to August 2013. RESULTS: The 5-y survival rate of the 274 ESCC subjects was 44.2%, with a median survival time of 44.12 mo. For the 274 ESCC subjects involved in the investigation of HOXC6 and HOXC8 expressions, the median survival time of subjects with high-level expressions of HOXC6 and HOXC8 was shorter than that for subjects with low-level expressions (P = 0.001, P < 0.001, respectively). Similar results were obtained from the analysis of the prognostic value of HOXC6 and HOXC8 in the group treated with surgery alone and the group treated with neoadjuvant chemotherapy. Multivariate analysis demonstrated that HOXC6 and HOXC8 expressions were independent prognostic factors in patients with ESCC. CONCLUSIONS: The HOXC6 and HOXC8 genes can be used as prognostic markers in patients with ESCC, but prospective studies are still needed to confirm.

A novel Dual-Branch Asymmetric Encoder-Decoder Segmentation Network for accurate colonic crypt segmentation.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with colonic crypts (CC) being crucial in its development. Accurate segmentation of CC is essential for decisions CRC and developing diagnostic strategies. However, colonic crypts' blurred boundaries and morphological diversity bring substantial challenges for automatic segmentation. To mitigate this problem, we proposed the Dual-Branch Asymmetric Encoder-Decoder Segmentation Network (DAUNet), a novel and efficient model tailored for confocal laser endomicroscopy (CLE) CC images. In DAUNet, we crafted a dual-branch feature extraction module (DFEM), employing Focus operations and dense depth-wise separable convolution (DDSC) to extract multiscale features, boosting semantic understanding and coping with the morphological diversity of CC. We also introduced the feature fusion guided module (FFGM) to adaptively combine features from both branches using cross-group spatial and channel attention to improve the model representation in focusing on specific lesion features. These modules are seamlessly integrated into the encoder for effective multiscale information extraction and fusion, and DDSC is further introduced in the decoder to provide rich representations for precise segmentation. Moreover, the local multi-layer perceptron (LMLP) module is designed to decouple and recalibrate features through a local linear transformation that filters out the noise and refines features to provide edge-enriched representation. Experimental evaluations on two datasets demonstrate that the proposed method achieves Intersection over Union (IoU) scores of 81.54% and 84.83%, respectively, which are on par with state-of-the-art methods, exhibiting its effectiveness for CC segmentation. The proposed method holds great potential in assisting physicians with precise lesion localization and region analysis, thereby improving the diagnostic accuracy of CRC.

The efficacy of immune checkpoint inhibitors therapy versus chemotherapy in the treatment of advanced and metastatic urothelial carcinoma: a meta-analysis.

PURPOSE: The application of platinum-based chemotherapeutic agents is the traditional treatment paradigm for advanced and metastatic urothelial carcinoma, which has changed with the advent of immune checkpoint inhibitors (ICIs). This study aims to evaluate the efficacy of ICI therapy versus chemotherapy in the treatment of advanced and metastatic urothelial carcinoma. METHODS: A systematic literature search of Web of Science, Embase, PubMed, and Cochrane Central Register of Controlled Trials was performed by two independent investigators. The primary endpoint was overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: The patients treated with ICI monotherapy had no significant difference in OS than those treated with chemotherapy monotherapy (HR: 0.965, 95% CI 0.865-1.076, p = 0.518). However, the patients treated with ICI monotherapy had a higher ORR and lower incidence of high-grade (≥ grade 3) AEs than those treated with chemotherapy monotherapy (OR: 0.568, 95% CI 0.479-0.675, p < 0.001; OR: 0.614, 95% CI 0.446-0.845, p = 0.003). The patients treated with ICI in combination with chemotherapy had significantly better OS and PFS than those treated with chemotherapy alone (HR: 0.862, 95% CI 0.776-0.957, p = 0.006; HR: 0.788, 95% CI 0.707-0.879, p < 0.001). However, there was no significant difference in ORR or the incidence of grade 3 or higher AEs (OR: 0.951, 95% CI 0.582-1.554, p = 0.841; OR: 0.942, 95% CI 0.836-1.062, p = 0.328). CONCLUSION: ICI monotherapy did not show statistically significant difference in OS but demonstrated higher ORR and lower incidence of high-grade (≥ grade 3) AEs. And a statistically significant OS and PFS benefit was found in patients treated with first-line ICI in combination with chemotherapy compared to chemotherapy alone.

Counterfactual Sepsis Outcome Prediction Under Dynamic and Time-Varying Treatment Regimes.

Sepsis is a life-threatening condition that occurs when the body's normal response to an infection is out of balance. A key part of managing sepsis involves the administration of intravenous fluids and vasopressors. In this work, we explore the application of G-Net, a deep sequential modeling framework for g-computation, to predict outcomes under counterfactual fluid treatment strategies in a real-world cohort of sepsis patients. Utilizing observational data collected from the intensive care unit (ICU), we evaluate the performance of multiple deep learning implementations of G-Net and compare their predictive performance with linear models in forecasting patient outcomes and trajectories over time under the observational treatment regime. We then demonstrate that G-Net can generate counterfactual prediction of covariate trajectories that align with clinical expectations across various fluid limiting regimes. Our study demonstrates the potential clinical utility of G-Net in predicting counterfactual treatment outcomes, aiding clinicians in informed decision-making for sepsis patients in the ICU.