Sodium fluoride-induced autophagy of ameloblast-like cells via the p-ULk1/ATG13/LC3B pathway in vitro.

OBJECTIVE: To investigate the effects of sodium fluoride on the ameloblast and reveal the mechanism of dental fluorosis. MATERIALS AND METHODS: Mouse ameloblast-like cell line (ALC) cells were treated with various concentrations of NaF, and subjected to Incucyte, fluorescence immunoassay, transmission electron microscopy, reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot for autophagy examination, alkaline phosphatase and alizarin red staining for mineralization after osteogenic induction. RESULTS: NaF exerts a dose-dependent inhibitory effect on ALC cell growth. TEM and fluorescence immunoassay showed that 1.5 mM or higher concentrations of NaF could induce a fusion of lysosome and mitochondria, finally increasing the number of autophagosome. RT-qPCR and western blot showed that the upregulation of autophagy related gene 13 (ATG13), downregulation of phosphorylated Unc-51-like kinase 1 (p-ULK1) were found in NaF-induced autophagy of ALC cells. The knockdown of ATG13 could rescue it as well as the expression of p-ULK1 and LC3B. Besides, alizarin red staining showed that fluoride under these concentrations could promote the mineralization of ALC. CONCLUSIONS: The data show that fluoride in higher concentration can induce autophagy via the p-ULk1/ATG13/LC3B pathway of ALCs than lower ones promote mineralization in vitro, which provides insight into the function of NaF in the autophagy and mineralization of ameloblast.

Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

The association between mammographic density and breast cancer molecular subtypes: a systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis to evaluate the whether high mammographic density (MD) is differentially associated with all subtypes of breast cancer. MATERIALS AND METHODS: The PubMed, Cochrane Library, and Embase databases were searched systematically in October 2022 to include all studies that investigated the association between MD and breast cancer subtype. Aggregate data of 17,193 breast cancer cases from 23 studies were selected, including five cohort/case-control and 18 case-only studies. The relative risk (RR) of MD were combined using random/fixed effects models for case-control studies, and for case-only studies, relative risk ratios (RRRs) were a combination of luminal A, luminal B, and HER2-positive versus triple-negative tumours. RESULTS: Women in the highest density category in case-control/cohort studies had a 2.24-fold (95% confidence interval [CI] 1.53, 3.28), 1.81-fold (95% CI 1.15, 2.85), 1.44-fold (95% CI 1.14, 1.81), and 1.59-fold (95% CI 0.89, 2.85) higher risk of triple-negative, HER-2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B breast cancer compared to women in the lowest density category. RRRs for breast tumours being luminal A, luminal B, and HER-2 positive versus triple-negative in case-only studies were 1.62 (95% CI 1.14, 2.31), 1.81 (95% CI 1.22, 2.71) and 2.58 (95% CI 1.63, 4.08), respectively, for BIRADS 4 versus BIRADS 1. CONCLUSION: The evidence indicates MD is a potent risk factor for the majority of breast cancer subtypes to different degrees. Increased MD is more strongly linked to HER-2-positive cancers compared to other breast cancer subtypes. The application of MD as a subtype-specific risk marker may facilitate the creation of personalised risk prediction models and screening procedures.

[Effect of high flow nasal catheter oxygen to prevent hypoxemia in endoscopic retrograde cholangiopancreatography surgery in aged].

Objective: To explore the effect of high-flow nasal catheter oxygen inhalation in preventing hypoxemia during endoscopic retrograde cholangiopancreatography (ERCP) surgery in elderly patients. Methods: From September 2021 to September 2022, 116 elderly patients (aged ≥ 70 years) who underwent elective ERCP in the Northern Theater General Hospital were prospectively selected, then divided into general nasal catheter oxygen inhalation group [group C, 31 males and 27 females, aged (79.8±6.4) years] and high-flow nasal catheter oxygen inhalation group [group H, 33 males and 25 females, aged (81.4±6.7) years], with 58 patients in each group. All patients were monitored for anesthesia by target-controlled infusion of propofol and remifentanil. The main outcome index was the incidence of intraoperative subclinical hypoxemia (90% ≤ SpO2 < 95%, duration >5 s), hypoxemia (75% < SpO2 < 90%, 5 s < duration ≤ 60 s) and severe hypoxemia (SpO2 < 75% or SpO2 < 90%, duration > 60 s). Secondary observation measures were SpO2 from T0 to T5 (T0, before anesthesia induction; T1, immediately after anesthesia induction; T2, endoscopic introduction; T3, duodenal papula intubation; T4, endoscopic withdrawal; T5, postoperative awakening), the arterial oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaCO2) and pH at T0, 15 min after the induction and T5. Results: The incidence of intraoperative subclinical hypoxemia in group C and group H was 12.0% (7/58) and 3.4% (2/58) respectively, which showed no significant statistical difference (P=0.165) from each other. The incidence of intraoperative hypoxemia in group H was 8.6% (5/58), which was significantly lower than 31.0% (18/58) of group C (P=0.003). Neither group had intraoperative severe hypoxemia. SpO2 of group H were (98.2±0.9)%, (98.2±0.9)%, (97.8±1.7)% and (97.7±1.7)% at T1, T2, T3, T4, which were higher than (96.8±2.1)%, (96.4±3.0)%, (96.1±2.9)% and (96.4±3.4)% in group C (all P<0.05). PaO2 at 15 min after induction in group H was (240.5±46.7) mmHg (1 mmHg=0.133 kPa), which was higher than that of group C (170.6±33.4) mmHg (P<0.001). There was no statistically significant difference in pH and PaCO2 between the two groups of patients at each timepoint. Conclusion: High flow nasal catheter oxygen can effectively reduce the incidence of hypoxemia in ERCP in elderly patients.

The Relationship between Choroidal Thickness and Liver Damage in Simple Auto-immune Hepatitis Patients.

BACKGROUND: There was no sufficient clinical evidence on the relationship between auto-immune hepatitis (AIH) and risk of eye illness, except 11 uveitis cases where related AIH is reported currently. AIM: To determine the relationship between choroidal thickness (ChT) and liver damage in simple AIH patients without ocular symptoms after oral prednisone treatment. PATIENTS AND METHODS: This prospective observational study included simple AIH patients. The patients' ChT was measured by swept-source (SS)-optical coherence tomography (OCT), and the liver damage was evaluated by alanine aminotransferase (ALT) and aspartate aminotransferase (AST). ChT and liver functions were assessed prior to and after treatment. Then comparisons were made prior to and post treatment. The relationships between biochemical indexes of liver injury and ChT were evaluated after a mean (SD) of 24 (1.28) weeks of regular oral prednisone. RESULTS: A total of 35 patients (31 females, aged 45.66 ± 11.62 years) were included. After treatment, ChT was significantly increased in all sectors (including the center sector, superior inner sector, inner nasal sector, inferior inner sector, inner temporal sector, superior outer sector, outer nasal sector, inferior outer sector, and outer temporal sector) (all P < 0.001). After treatment, both ALT (51.34 ± 44.16 vs 255.06 ± 107.84, P < 0.001) and AST (38.66 ± 27.12 vs 164.89 ± 85.58, P < 0.001) were significantly decreased. The increase of ChT in all sectors was significantly related to the decrease of ALT and AST (all P < 0.001). CONCLUSION: The improvement of ChT might reflect the remission of liver damage in simple AIH patients without ocular symptoms during oral prednisone treatment.

[Relationship between valve ablation and bladder function in children with posterior urethral valves disorder].

This study is to investigate the effect of valve ablation on bladder function in patients with posterior urethral valves. The clinical data of patients with posterior urethral valves who received urodynamic examination before and after valve ablation were retrospectively analyzed.The bladder compliance improved during urine storage after operation, and the maximum detrusor pressure decreased during micturition. The postoperative urinary system ultrasound showed that the residual urine volume of the group with significantly improved upper urinary tract hydrocephalus was significantly less than that of the group with no improvement. The bladder compliance was significantly higher than that of the group with no improvement, and the maximum urine flow rate was significantly higher than that of the group with no improvement (all P<0.05). Valve ablation has limited effect on improving bladder function in patients with PUV. Valve incision can help improve the maximum bladder volume, residual urine volume and maximum urinary flow rate. It has a certain effect on bladder compliance and maximum detrusor pressure.

[Free anterolateral thigh myocutaneous flap combined with pedicled latissimus dorsi myocutaneous flap transfer for functional reconstruction after resection of huge shoulder tumor].

Objective: To investigate the method and effect of free anterolateral thigh myocutaneous flap combined with pedicled latissimus dorsi myocutaneous flap transfer for functional reconstruction after resection of huge shoulder tumor. Methods: The clinical data of 6 patients who were treated with pedicled latissimus dorsi myocutaneous flap combined with free anterolateral thigh myocutaneous flap to repair large-area complex defects after shoulder tumor resection at Department of Oncology Plastic Surgery, Hunan Province Cancer Hospital from December 2015 to December 2020 were retrospectively analyzed. There were 2 males and 4 females, with an average age of 41.7 years (range:29 to 56 years). There were 2 cases of synovial sarcoma,2 cases of phylloid cell sarcoma,1 case of liposarcoma and 1 case of fibrosarcoma. Before this operation, tumor resection had been performed for 1 to 5 times on each case,and the course of disease was 6 to 24 months. Pedicled latissimus dorsi myocutaneous flap combined with free anterolateral thigh myocutaneous flap were used to repair soft tissue defects and reconstruct deltoid function. Postoperative flap status, complications, appearance and function of upper limbs and tumor recurrence were recorded. Results: Six patients were followed up for an average of 21.6 months (range: 12 to 36 months). There were no serious complications after operation,and all flaps survived. No tumor recurrence was found. The appearance of shoulder contour reconstructed by flaps was satisfactory. The reinnervation effect of lateral femoral muscle was confirmed recovered smoothly by neuroelectromyography 3 months after operation. Shoulder function was mildly limited in 3 patients,moderately limited in 2 patients and severely limited in 1 patient. All patients reported significant improvement in shoulder discomfort.The overall functional results of all patients were satisfactory. Conclusion: Combined myocutaneous flaps transplantation can perfectly repair the wound left after the resection of huge shoulder tumor,minimize the recurrence of tumor,reconstruct the function of shoulder joint and greatly improve the quality of life of patients.

Intrinsic Spin Susceptibility and Pseudogaplike Behavior in Infinite-Layer LaNiO_{2}.

The recent discovery of superconductivity in doped infinite-layer nickelates has stimulated intensive interest, especially for similarities and differences compared to that in cuprate superconductors. In contrast to cuprates, although earlier magnetization measurement reveals a Curie-Weiss-like behavior in undoped infinite-layer nickelates, there is no magnetic ordering observed by elastic neutron scattering down to liquid helium temperature. Until now, the nature of the magnetic ground state in undoped infinite-layer nickelates was still elusive. Here, we perform a nuclear magnetic resonance (NMR) experiment through ^{139}La nuclei to study the intrinsic spin susceptibility of infinite-layer LaNiO_{2}. First, the signature for magnetic ordering or freezing is absent in the ^{139}La NMR spectrum down to 0.24 K, which unambiguously confirms a paramagnetic ground state in LaNiO_{2}. Second, a pseudogaplike behavior instead of Curie-Weiss-like behavior is observed in both the temperature-dependent Knight shift and nuclear spin-lattice relaxation rate (1/T_{1}), which is widely observed in both underdoped cuprates and iron-based superconductors. Furthermore, the scaling behavior between the Knight shift and 1/T_{1}T has also been discussed. Finally, the present results imply a considerable exchange interaction in infinite-layer nickelates, which sets a strong constraint for the proposed theoretical models.

[Quality of life of patients with primary open-angle glaucoma based on EQ-5D in Wenzhou].

Objective: To evaluate the quality of life of patients with primary open-angle glaucoma (POAG) and its related factors in Wenzhou. Methods: Cross-sectional analysis. A total of 339 POAG patients diagnosed in the Wenzhou glaucoma progression study conducted in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University from March 2014 to October 2019 were included. Quality of life of POAG patients was assessed by EQ-5D including the visual analogue scale (VAS). The effects of gender, age, visual field loss (VFL), family history of glaucoma, hypertension, diabetes, migraine, sleep quality, and amateur exercise on the quality of life were analyzed. The utility value (UV) and VAS score were expressed as the median (P25, P75), and Mann-Whitney U was used for the comparison between two groups. Kruskal-Wallis H was performed to compare the differences among multiple groups. Results: A total of 339 POAG patients were included in the study; 164 were males (48.4%), and 175 were females (51.6%). The mean age was (63±10) years. Thirty-four patients (10.0%) had received medication (including one with combined surgical treatment), while the remaining 305 patients (90.0%) had received no anti-glaucoma treatment. Among the patients, 10.5% (32/305) had no VFL, 68.9% (210/305) had mild VFL, 17.0% (52/305) had moderate VFL, and 3.6% (11/305) had severe VFL. In all patients, the median of UV was 1.000 (1.000, 1.000), the mean of UV was 0.964, and the median of VAS score was 80 (75, 90), the mean of VAS score was 81.58. Anxiety or depression and pain or discomfort occurred in 45.7% (43/94) and 34.1% (32/94), respectively, of POAG patients with decreased UVs, as well as mobility constraints in 13.8 % (13/94) and usual activity constraints in 6.4% (6/94). The median of UV of the eye with a better visual field in the group without VFL or with mild or moderate VFL was 1.000 (1.000, 1.000), and in the group with severe VFL was 1.000 (0.862, 1.000), but there was no significant difference in the UV and the VAS score of the eye with a better visual field among groups with different degrees of VFL (both P>0.05). There was statistically significant difference in the UV among groups with different sleep qualities (H=17.465; P<0.01). Using pairwise comparison, the median of UV of the very good sleep group was 1.000 (1.000, 1.000), significantly different to the slightly poor sleep group 1.000 (0.866, 1.000) (z=3.613; P<0.05). The median of UV in patients with migraine was 1.000 (0.875, 1.000), without migraine 1.000 (1.000, 1.000), and in patients with hypertension was 1.000 (0.875, 1.000), without hypertension 1.000 (1.000, 1.000), and in patients with diabetes was 1.000 (0.875, 1.000), without diabetes was 1.000 (1.000, 1.000), the difference was statistically significant (Z=-2.189, -3.864, -2.417; all P<0.05). The UV was not related to age, gender, family history of glaucoma, amateur exercise, alcohol and tobacco, and history of anti-glaucoma medication (all P>0.05). Conclusions: VFL is related to the UV of POAG patients in Wenzhou. Quality of life in mild POAG patients is good but decrease in advanced POAG patients. Sleep quality, systemic complications and physical or psychological discomfort impact on quality of life in POAG patients. (Chin J Ophthalmol, 2021, 57: 207-214).

Preformed Cooper Pairs in Layered FeSe-Based Superconductors.

Superconductivity arises from two distinct quantum phenomena: electron pairing and long-range phase coherence. In conventional superconductors, the two quantum phenomena generally take place simultaneously, while in the underdoped high- T_{c} cuprate superconductors, the electron pairing occurs at higher temperature than the long-range phase coherence. Recently, whether electron pairing is also prior to long-range phase coherence in single-layer FeSe film on SrTiO_{3} substrate is under debate. Here, by measuring Knight shift and nuclear spin-lattice relaxation rate, we unambiguously reveal a pseudogap behavior below T_{p}∼60 K in two kinds of layered FeSe-based superconductors with quasi2D nature. In the pseudogap regime, a weak diamagnetic signal and a remarkable Nernst effect are also observed, which indicates that the observed pseudogap behavior is related to superconducting fluctuations. These works confirm that strong phase fluctuation is an important character in the 2D iron-based superconductors as widely observed in high-T_{c} cuprate superconductors.

Detection of Acoustic Plasmons in Hole-Doped Lanthanum and Bismuth Cuprate Superconductors Using Resonant Inelastic X-Ray Scattering.

High T_{c} superconductors show a rich variety of phases associated with their charge degrees of freedom. Valence charges can give rise to charge ordering or acoustic plasmons in these layered cuprate superconductors. While charge ordering has been observed for both hole- and electron-doped cuprates, acoustic plasmons have only been found in electron-doped materials. Here, we use resonant inelastic x-ray scattering to observe the presence of acoustic plasmons in two families of hole-doped cuprate superconductors (La_{1.84}Sr_{0.16}CuO_{4} and Bi_{2}Sr_{1.6}La_{0.4}CuO_{6+δ}), crucially completing the picture. Interestingly, in contrast to the quasistatic charge ordering which manifests at both Cu and O sites, the observed acoustic plasmons are predominantly associated with the O sites, revealing a unique dichotomy in the behavior of valence charges in hole-doped cuprates.

Differentiation of follicular carcinomas from adenomas using histogram obtained from diffusion-weighted MRI.

AIM: To evaluate the role of histogram analysis of apparent diffusion coefficient (ADC) maps from diffusion-weighted imaging (DWI) in the differentiation of follicular thyroid carcinoma (FTC) from follicular adenoma (FA) in nodules indeterminate on ultrasound-guided core needle biopsy (USCNB). MATERIALS AND METHODS: This study was performed with institutional review board approval. Seventeen patients who were planned to undergo diagnostic lobectomy for an indeterminate thyroid nodule (atypical of unknown significance/follicular lesion of undetermined significance [AUS/FLUS] or suspicious for follicular neoplasm/follicular neoplasm [SFN]) on USCNB were enrolled prospectively. All patients underwent DWI on the day before surgery. Histogram parameters were derived from ADC values obtained from the whole extent of the tumours. The parameters were compared with the final diagnosis based on histopathological examination after surgery. The accuracy of the parameters in differentiating FTC from FA was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Twelve patients were confirmed as having FA and five patients as having FTC. Histogram parameters including the 10th (ADC10), 25th (ADC25), and 50th (ADC50) percentiles of the ADC values were significantly lower in FA than in FTC (p < 0.05, all). ROC curve analysis revealed that ADC25 resulted in the highest AUC (0.867; confidence interval, 0.616-0.980), with a cut-off value of 0.352×10-3 mm2/s. CONCLUSION: Histogram parameters from ADC maps could differentiate FTC from FA effectively in indeterminate nodules on USCNB, with ADC25 being the most promising parameter.

The use of a synthetic shoulder patch for large and massive rotator cuff tears - a feasibility study.

BACKGROUND: The aim of this study was to explore the feasibility of using a non-absorbable biocompatible polyester patch to augment open repair of massive rotator cuff tears (Patch group) and compare outcomes with other treatment options (Non-patch group). METHODS: Participants referred to orthopaedic clinics for rotator cuff surgery were recruited. Choice of intervention (Patch or Non-patch) was based on patient preference and intra-operative findings. Oxford Shoulder Score (OSS), Shoulder Pain and Disability Index (SPADI), and Constant score were completed at baseline and 6 months. Shoulder MRI was performed at baseline and 6 months to assess fat fraction and Goutallier classification pre- and post- treatment. Feasibility outcomes (including retention, consent and missing data) were assessed. RESULTS: Sixty-eight participants (29 in the Patch group, 39 in Non-patch group) were included (mean age 65.3 years). Conversion to consent (92.6%), missing data (0% at baseline), and attrition rate (16%) were deemed successful feasibility endpoints. There was significant improvement in the Patch group compared to Non-patch at 6 months in OSS (difference in medians 9.76 (95% CI 2.25, 17.29) and SPADI: 22.97 (95% CI 3.02, 42.92), with no substantive differences in Constant score. The patch group had a higher proportion of participants improving greater than MCID for OSS (78% vs 62%) and SPADI (63% vs 50%) respectively. Analysis of the 48 paired MRIs demonstrated a slight increase in the fat fraction for supraspinatus (53 to 55%), and infraspinatus (26 to 29%) at 6 months. These differences were similar and in the same direction when the participants were analysed by treatment group. The Goutallier score remained the same or worsened one grade in both groups equally. CONCLUSIONS: This study indicates that a definitive clinical trial investigating the use of a non-absorbable patch to augment repair of massive rotator cuff tears is feasible. In such patients, the patch has the potential to improve shoulder symptoms at 6 months. TRIAL REGISTRATION: ISRCTN, ISRCTN79844053, Registered 15th October 2014 (retrospectively registered).

Coronal root canal morphology of permanent two-rooted mandibular first molars with novel 3D measurements.

AIM: To measure the coronal root canal morphology of permanent mandibular first molars using 3D coordinates for more precise conservative endodontic cavity preparation. METHODOLOGY: In total, 57 cone beam computed tomography (CBCT) images of sound mandibular molars with fully formed apices without previous endodontic treatment were taken from 33 patients aged 16 to 75 years. The CBCT machine (MCT-1[EX-2F], J. Morita Manufacturing Corp, Kyoto, Japan) provided 14-bit greyscale images with the voxel size of 0.125 mm. All images were taken at 80 kV and 5.0 mA, with a 17-s exposure time, which were then reconstructed in 3D models and viewed by an endodontist. The gender of the patients and the tooth position, and number of root canals, were recorded. The landmarks of coronal root canals were determined, then the distribution of landmarks, maximum curvature in the axial direction and curvature directions in the horizontal direction of coronal root canals were measured. Distributions of landmarks were analysed using a spatial statistics method. Data about curvature were compared using a t test. RESULTS: Overall, the distribution of root canal orifices and the centre of the canal primary curve were more centralized than other landmarks. The landmarks were located more mesiobuccally to the centre of the occlusal plane of mandibular first molars. Specifically, the measurements of the maximum curvature of coronal root canals in the axial direction were as follows: in 3-canal teeth, the average angles of curvatures were 22°,23°,15° for mesiobuccal (MB), mesiolingual (ML) and distobuccal (DB) canals, respectively; in 4-canal teeth, the average angles of curvatures were 24°,26°,15°,22°for MB, ML, DB and distolingual (DL) canals, respectively. The degrees of coronal root canal curvatures in the horizontal direction were as follows: in 3-canal teeth, the average angles of curvatures were -8°,47°,-2° for MB, ML and DB canals, respectively; in 4-canals teeth, the average angles were -11°,50°,-28°,45° for MB, ML, DB and DL canals, respectively. Statistically, there was no reliable side or sex difference in any of the measurements (P > 0.05). CONCLUSIONS: In permanent two-rooted mandibular first molars, the coronal canals clustered in the direction of the mesiobuccal side of the occlusal surface of the teeth.

[A preliminary study on molecular target identification of drugs in individualized treatment of malignant solid tumors in children].

Objective: To explore the role of drug-related molecular target identification in the individualized treatment of malignant solid tumors in children. Methods: The clinical data of 40 patients diagnosed with malignant solid tumors from Beijing Tongren Hospital, Capital Medical University, between June 2017 and March 2019 were retrospectively analyzed. Immunohistochemistry, polymerase chain reaction and sequencing methods were used to determine the expression levels and mutations of tumor drug molecular targets, and to compare the efficiency as well as the incidence of toxic side effects of chemotherapy using anti-tumor drugs with various molecular targets. Results: A total of 4 tumor drug-related targets were identified in 40 tumor tissue samples, namely DNA topoisomerase-ⅡA (TOPOⅡA), ß(3)-tubulin (Tubulinß(3)), DNA topoisomerase-Ⅰ(TOPOⅠ) and dihydrofolate reductase gene polymorphisms [DHFR (C829T)]. The effective rates of platinum-based agents, methotrexate, irinotecan, vinblastine and anthracycline for malignant solid tumors in children were 90.0% (36/40), 85.0% (34/40), 70.0% (28/40), 67.5% (27/40), 62.5% (25/40), respectively. The effective rates of chemotherapy with irinotecan, methotrexate, and vinblastine in mesenchymal tumors were 68.9% (20/29), 62.1% (18/29), 68.9% (20/29), respectively, which were considerably higher than 18.2% (2/11), 36.4% (4/11) and 36.4% (4/11) in non-mesenchymal tumors, with significant differences (χ(2)=5.487, 15.345, 17.278, all P<0.05). The effective rate of chemotherapy of platinum-based drugs for non-mesenchymal tumors was 72.3% (8/11), which was significantly higher than 58.6% (17/29) in mesenchymal tumors, and the difference was statistically significant (χ(2)=11.231, P<0.05). The intensity of toxic side effects in order from high to low was anthracycline > platinum > methotrexate > vinblastine > irinotecan. Conclusion: Tumor drug-related molecular targets and the sensitivity of tumors of different origins to the same anti-tumor drug as well as side effects are predicted, which provides a theoretical and clinical basis for individualized treatment of malignant tumors in children.

[Robotic hilar cholangiocarcinoma radical resection compared with laparotomy in prognosis].

Objective: To compare the long term and short term outcomes between robotic and open surgery for hilar cholangiocarcinoma radical resection. Methods: This is a single-center and retrospective case-control study. Patients underwent hilar cholangiocarcinoma radical resection between January 2016 and December 2016 at Department of Hepatobiliary Surgery of the General Hospital of the Chinese People's Liberation Army were included. Safety, effectiveness and long-term prognosis of tumors were evaluated. Patients were divided into robotic hilar cholangiocarcinoma radical surgery group (robotic group, n=16) and open hepatic hilar cholangiocarcinoma radical surgery group (open group, n=31) . All cases were confirmed by pathology histological. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS) , and overall survival (OS) were retrospectively collected and analyzed.In the follow-up cohort, the primary outcome was patient death and the secondary outcome was tumor recurrence. Continuous variables were expressed as means and medians and were compared using the Student t test if normally distributed or Wilcoxon-Mann-Whitney test for nonparametric variables. Discrete variables were expressed as frequency and percentages and χ(2) or Fisher exact test, when appropriate, were used for comparisons. Kaplan-Meier curves were used to calculate the probability of survival and comparisons were performed using log-rank test. Results: In this study, compared with the open group, the robotic group had a longer operation time ( (338±71) minutes vs. (256±56) minutes, t=4.251, P=0.001) , but the intraoperative blood loss was less (100 ml vs. 200 ml, Z=121.50, P=0.040) , the gastric tube removal time was earlier (3 days vs. 4 days, Z=136.0, P=0.011) , and the postoperative hospital stay was shorter (9 days vs. 12 days, Z=144.50, P=0.040) , and the difference was statistically significant.There was no significant difference in the blood transfusion rate, R0 resection rate, and tumor size between the two groups.The recurrence rates in the robotic group and open surgery were 53.3% and 67.0%, respectively (χ(2)=1.04, P=0.307) .The median survival time of the robotic group and the open group was 22.0 months and 25.0 months. There was no significant difference in the overall survival rate between the two groups (P>0.05) . Conclusion: Compared with laparotomy, robotic HCC radical resection could have an equivalence or non-inferiority approach with acceptable long-term outcome.

Length of hospital stay after hip fracture surgery and 1-year mortality.

There is ongoing effort to discharge patients early after hip fracture surgery to reduce the medical and economic burden. We tried to find whether there is any related side effect, and discovered that early discharge, especially before 10 days after surgery, is associated with higher mortality. INTRODUCTION: The aim of this study was to analyze the association between the length of hospital stay after hip fracture and 1-year mortality in older adults aged ≥ 65 years old. METHODS: We conducted a retrospective cohort study using the Korean National Health Insurance Service data to identify patients who were discharged after hip fracture surgery from 2007 to 2009 among 487,460 older adults of age ≥ 65 years. The lengths of stay involving hip fracture surgery were categorized at 10-day interval, and analyzed in relation to 1-year mortality from the date of hospital discharge. RESULTS: A total of 4213 patients were discharged after hip fracture surgery, of whom 604 (14.3%) died within 1 year of discharge. The average length of stay was 30.7 days (standard deviation 24.5 days). The 1-year mortality was the highest for the length of stay ≤ 10 days group at 21.7%, followed by 15.2%, 14.3%, 13.3%, and 12.4% for > 40, 21-30, 31-40, and 11-20 days groups, respectively (p value 0.05). On Cox proportional hazard regression, the adjusted hazard ratio for length of stay ≤ 10 days group was 1.56 (95% confidence interval 1.14-2.12) against the reference group (11-20 days), while other groups did not show statistical significance. Higher risk of death was associated with increasing age, male gender, Charlson comorbidity index ≥3, subtrochanteric fracture, and discharge to tertiary care hospitals and long-term care hospitals. CONCLUSION: Older adults discharged within 10 days of hospital admission for hip fracture surgery have higher 1-year mortality after discharge.

Recommended pre-analytical plasma glucose sampling methodology may distort gestational diabetes mellitus prevalence: implications for diagnostic thresholds.

AIM: Current International Association of the Diabetes and Pregnancy Study Groups/World Health Organization gestational diabetes mellitus (GDM) diagnostic thresholds are based on a landmark study in which the pre-analytical plasma glucose sampling methodology is unclear. Worldwide, plasma glucose pre-analytical sampling methodology practices are divergent. We considered the effects of pre-analytical plasma glucose sampling methodology on GDM prevalence and gestational outcomes. METHODS: This is a retrospective observational cohort study of 1178 pregnant women undergoing an oral glucose tolerance test (OGTT). Of the 1178 pregnant women, a subset of 892 non-GDM women with singleton births undergoing OGTT between 24 and 28 weeks' gestation were investigated for large for gestation age (LGA) outcomes. OGTT were determined using traditional methods (sodium fluoride tubes batched at roomed temperature). We modelled the potential effects of using a recommended pre-analytical plasma glucose methodology (lyophilized citrate tubes) on GDM prevalence. RESULTS: The GDM prevalence in our cohort was 13.5%. The incidence of LGA showed a linear association with maternal plasma glucose that was similar to the association observed in the Hyperglycemia and Adverse Pregnancy Outcome study. Frequency of LGA exceeded 10% at HAPO glucose category 4 (fasting, 4.8 to 4.9 mmol/l; 1-h, 8.7 to 9.5 mmol/l) for fasting and 1-h plasma glucose. The use of a recommended pre-analytical method is projected to increase the prevalence of GDM to 39.2%. CONCLUSION: We challenge the consensus that recommended pre-analytical plasma glucose methodologies are optimal for the accurate diagnosis of GDM. Recommended pre-analytical plasma glucose methods may profoundly over-diagnose GDM. Centres using recommended pre-analytical plasma glucose methodologies may need to reappraise their diagnostic thresholds.

Solution-Processed Organic Photodetector Using Hafnium Oxide as an Electron Blocking Layer.

Organic photodetector (OPD) performance is affected significantly by leakage current. In this study, to decrease OPD leakage current, we introduced hafnium oxide as an electron blocking material, using a solution fabrication process. We fabricated an OPD consisting of ITO/HfO2/PCHT:PC60BM/Yb/Al, and measured its J-V characteristics, external quantum efficiency, and transient photocurrents. We found that the thickness of the hafnium oxide layer affected the detectivity of the prepared OPD. In particular, a device having an ultrathin hafnium oxide film (5.5 nm thick) exhibited a high on-off current ratio of up to 2.26 × 105 at -1 V, which is two times higher than that of a device having a PEDOT:PSS electron blocking layer.

NLRP6 suppresses the inflammatory response of human periodontal ligament cells by inhibiting NF-κB and ERK signal pathways.

AIM: To explore the function and mechanisms of NLRP6 (NOD-, LRR- and pyrin domain-containing 6) in the inflammatory response of human periodontal ligament cells (HPDLCs). METHODOLOGY: Tissues associated with apical periodontitis were obtained from three patients who underwent endodontic microsurgery. The expression of NLRP6 in 3 human apical periodontitis tissues and HPDLCs was examined by immunohistochemistry and immunofluorescence, respectively. The expressions of NLRP6, Phospho(p)- p65, p65, IκB-α, p- IκB-α, ERK, p- ERK, NLRP3, Pro interleukin (IL)-1ß, Pro caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) were examined by western blot. The gene expression and secretion of proinflammatory cytokines were detected using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Data were analysed statistically with independent sample t-tests. RESULTS: NLRP6 was expressed in inflammatory periapical tissues and HPDLCs. Lipopolysaccharide (LPS) from Escherichia coli induced NLRP6 in HPDLCs (P < 0.05). After silencing NLRP6, E. coli LPS-induced activation of NF-κB and ERK signalling was enhanced, which was also accompanied by elevated levels of IL-6 and tumour necrosis factor-α (TNF-α) (P < 0.05). Moreover, knockdown of NLRP6 led to up-regulation of NLRP3, Pro IL-1ß and Pro caspase-1 (P < 0.05), whereas down-regulation of ASC (P < 0.05), which may contribute to unchanged levels of IL-1ß in HPDLCs inflammation. CONCLUSION: NLRP6 was functionally expressed in inflamed periapical tissues and HPDLCs. NLRP6 negatively regulated the production of IL-6 and TNF-α in HPDLCs inflammation by inhibiting NF-κB and ERK signal pathways.