[A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma].

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Biological Properties of 3D-Printed Zirconia Implants with p-Cell Structures.

Research on 3-dimensional (3D) printed porous zirconia-based dental implants is still in its infancy. This study aimed to evaluate the biological responses of novel zirconia implants with p-cell structures fabricated by 3D printing. The solid zirconia samples exhibited comparable density, 3-point flexural strength, and accelerated aging properties compared to specimens prepared previously by conventional methods. Cell-based experiments showed that the p-cell structure promoted cell proliferation, adhesion, and osteogenesis-related protein expression. Mechanical tests showed that both p-cell and control implants could withstand a torque of 35 Ncm without breaking. The mean maximum breaking loads of p-cell and control implants were 1,222.429 ± 115.591 N and 1,903.857 ± 250.673 N, respectively, which were much higher than the human physiological chewing force and human mean maximum occlusal force. An animal experiment showed that the bone trabeculae around the implants were significantly thicker, more numerous, and denser in the p-cell group than in the control group. This work could provide promising guidance for further exploring 3D printing techniques for porous zirconia bionic implants in dentistry.

Measurement of the

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

Deep Underground Laboratory Measurement of

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

Direct Measurement of the Astrophysical

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

Application of artificial intelligence in diagnosis of osteoporosis using medical images: a systematic review and meta-analysis.

Artificial intelligence (AI) is a potentially reliable assistant in the diagnosis of osteoporosis. This meta-analysis aims to assess the diagnostic accuracy of the AI-based systems using medical images. We searched PubMed and Web of Science from inception to June 15, 2020, for eligible articles that applied AI approaches to diagnosing osteoporosis using medical images. Quality and bias of the included studies were evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The main outcome was the sensitivity and specificity of the performance of the AI-based systems. The data analysis utilized the R Foundation packages of "meta" for univariate analysis and Stata for bivariate analysis. Random effects model was utilized. Seven studies with 3186 patients were included in the meta-analysis. The overall risk of bias of the included studies was assessed as low. The pooled sensitivity was 0.96 (95% CI 0.93-1.00), and the pooled specificity was 0.95 (95% CI 0.91-0.99). However, high heterogeneity was found in this meta-analysis. The results supported that the AI-based systems had good accuracy in diagnosing osteoporosis. However, the high risk of bias in patient selection and high heterogeneity in the meta-analysis made the conclusion less convincing. The application of AI-based systems in osteoporosis diagnosis needs to be further confirmed by more prospective studies in multi-centers including more random samples from complete patient types.

Graphene Oxide Enables the Reosteogenesis of Previously Contaminated Titanium In Vitro.

The main goal of peri-implantitis treatment is to control infection and arrest bone loss, which requires the removal of polymicrobial biofilms on the implant surface and the reduction of tissue invasion. Additionally, prognosis can be improved if reosseointegration occurs on previously contaminated implants. To evaluate whether graphene oxide (GO) can remove polymicrobial biofilms, biofilms were established on titanium surfaces in vitro and treated with different methods: group B, removed only with brushing; group G, treated with different GO concentrations (64, 128, 256, and 512 µg/mL); group GB, combined treatments of groups B and G; and group C, untreated. Subsequently, to evaluate reosteogenesis on previously contaminated titanium, 4 groups were used: groups C, B, GB-256, and GB-512 (treated with 256 and 512 µg/mL of GO, respectively). Intact clean titanium (IC) was used as a control. Additionally, cell behavior on IC treated with GB-256 (IGB-256) and GB-512 (IGB-512) was compared with that of the GB-256 and GB-512 groups, respectively. The results showed that at high concentrations (≥256 µg/mL), GO eliminated residual bacteria and inhibited biofilm reformation after brushing, whereas neither GO nor brushing alone could achieve this. Bone marrow-derived mesenchymal stem cell viability in groups GB-256 and IC was higher than that in groups GB-512, C, and B (P < 0.05). No significant difference was found between group GB-256 and group IC (P > 0.05). Osteogenic differentiation of bone marrow-derived mesenchymal stem cells in group GB-256 was higher than that in groups IC, GB-512, C, and B. No difference was found between groups IGB-256 and IGB-512 and groups GB-256 and GB-512, respectively (P > 0.05). In conclusion, 256 µg/mL of GO combined with brushing significantly removed polymicrobial biofilms that remained on the previously contaminated titanium surfaces. The bone marrow-derived mesenchymal stem cell osteogenic potential was regained or even enhanced on the titanium surfaces treated this way in vitro, which might provide a new idea for treating peri-implantitis.

[Application of negative molds technology based on three-dimensional printing in digital maxillofacial prostheses].

Objective: To explore a digital negative molds technique based on three-dimensional (3D) printing to assist in the manufacture of maxillofacial prostheses, and to improve the deficiency of the current clinical treatment. Methods: Seventeen patients with maxillofacial defects (including nasal defects, orbital defects, cheek defects, auricle defect) were scanned by means of facial optical scanning and computer tomography (CT). The 3D models were then reconstructed and global registration was made to merge the reconstructed models into a new digital model for 3D design. The 3D design of the prostheses was implemented in software. The mechanical connection structure was designed by forward engineering technology for 3 patients with intra-oral defects in maxilla who needed to make removable partial dentures, so that the silicone prostheses and removable partial denture could be combined. The removable partial dentures were made by conventional method and connected with the prostheses. According to the 3D data of the prostheses, the digital negative molds were designed, and the 3D printing technology was used to finish the processing of the resin molds. Silicone for prostheses were filled and cured in the resin molds to fabricate the clinical restorations for the patients. The margin adaptation and retention of the prostheses was detected. Results: Twenty patients with varying degrees of maxillofacial defects were rehabilitated using the courses developed in the study. All patients reported no pain or discomfort during the treatment; and they were satisfied with the final prostheses of the shape, color, retention, stability, etc. Eighteen of the prostheses showed good marginal adaptation, and sixteen of the prostheses showed good retention effect. Conclusions: The digital negative molds technique used in this study could greatly reduce the intensity of manual operation and provided a good therapeutic effect for patients with maxillofacial defects.

Efficacy and safety of interleukin-17 antagonists in patients with plaque psoriasis: a meta-analysis from phase 3 randomized controlled trials.

BACKGROUND: The interleukin-17 (IL-17) cytokine pathway plays a key role in the development of psoriasis. Antibodies targeting IL-17 or blocking its receptor may be a new therapeutic approach for psoriasis. To assist treatment selection in daily practice, it is essential to understand the benefit and risk profile of IL-17 antagonists. OBJECTIVE: We performed a meta-analysis to evaluate the efficacy and safety of IL-17 antagonists in patients with psoriasis. METHODS: We searched a number of databases for relevant randomized controlled trials (RCTs) published before May 2016. The following outcomes were evaluated: Psoriasis Area and Severity Index (PASI) 75, 90, 100 response, Investigator's Global Assessment (IGA) score of 0 or 1 response, adverse events (AEs) and withdrawals. The meta-analysis was performed using Review Manager 5.2 software. RESULTS: Nine RCTs with 5951 patients were included. IL-17 antagonists achieved higher PASI 75, 90, 100 response rates and Dermatology Life Quality Index 0 or 1 response rates than placebo and a lower incidence of discontinuations due to lack of efficacy. In the safety analysis, no significant differences were found between the IL-17 antagonists and placebo in the proportion of patients with serious AEs, cardiovascular disease and discontinuations due to AEs. However, IL-17 antagonists were associated with a higher proportion of patients with any AEs and infections than placebo. CONCLUSION: IL-17 antagonists were effective, with an acceptable safety profile, for patients with plaque psoriasis. Vigilance because of the potential for infection will be necessary for IL-17 antagonists.

[Application of ARIMA model to predict number of malaria cases in China].

Objective To study the application of autoregressive integrated moving average (ARIMA) model to predict the monthly reported malaria cases in China, so as to provide a reference for prevention and control of malaria. Methods SPSS 24.0 software was used to construct the ARIMA models based on the monthly reported malaria cases of the time series of 20062015 and 2011-2015, respectively. The data of malaria cases from January to December, 2016 were used as validation data to compare the accuracy of the two ARIMA models. Results The models of the monthly reported cases of malaria in China were ARIMA (2, 1, 1) (1, 1, 0)12 and ARIMA (1, 0, 0) (1, 1, 0)12 respectively. The comparison between the predictions of the two models and actual situation of malaria cases showed that the ARIMA model based on the data of 2011-2015 had a higher accuracy of forecasting than the model based on the data of 2006-2015 had. Conclusion The establishment and prediction of ARIMA model is a dynamic process, which needs to be adjusted unceasingly according to the accumulated data, and in addition, the major changes of epidemic characteristics of infectious diseases must be considered.

Haploinsufficiency caused by a nonsense mutation in NCSTN underlying hidradenitis suppurativa in a Chinese family.

Hidradenitis suppurativa (HS) is a chronic disease of follicular occlusion. It involves the axilla, groin, perianal and perineal regions, and is characterized by recurrent draining sinuses, skin abscesses and disfiguring scars. Loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of HS. We collected skin samples from three patients with HS from a Chinese family carrying a NCSTN mutation (c.1258C>T (p.Q420X)) and three unrelated healthy controls (HCs). Expression level of nicastrin in skin tissue and cultured keratinocytes and fibroblasts of patients and HCs was determined by real-time quantitative PCR and western blotting. We found that the mRNA and protein levels of nicastrin were significantly reduced in the whole skin, epidermis, dermis, and cultured keratinocytes and fibroblasts compared with HCs. Therefore, we conclude that haploinsufficiency of the NCSTN gene caused by the nonsense mutation c.1258C>T (p.Q420X) contributes to the occurrence of HS in this family.

Screening drug target proteins based on sequence information.

Identifying new drug target (DT) proteins is important in pharmaceutical and biomedical research. General machine learning method (GMLM) classifiers perform fairly well at prediction if the training dataset is well prepared. However, a common problem in preparing the training dataset is the lack of a negative dataset. To address this problem, we proposed two methods that can help GMLM better select the negative training dataset from the test dataset. The prediction accuracy was improved with the training dataset from the proposed strategies. The classifier identified 1797 and 227 potential DT proteins, some of which were mentioned in previous research, which added correlative weight to the new method. Practically, these two sets of potential DT proteins or their homologues are worth considering.

Load transfer characteristics of unilateral distal extension removable partial dentures with polyacetal resin supporting components.

BACKGROUND: To photoelastically examine load transfer by unilateral distal extension removable partial dentures with supporting and retentive components made of the lower stiffness polyacetal resins. METHODS: A mandibular photoelastic model, with edentulous space distal to the right second premolar and missing the left first molar, was constructed to determine the load transmission characteristics of a unilateral distal extension base removable partial denture. Individual simulants were used for tooth structure, periodontal ligament, and alveolar bone. Three designs were fabricated: a major connector and clasps made from polyacetal resin, a metal framework as the major connector with polyacetal resin clasp and denture base, and a traditional metal framework I-bar removable partial denture. Simulated posterior bilateral and unilateral occlusal loads were applied to the removable partial dentures. RESULTS: Under bilateral and left side unilateral loading, the highest stress was observed adjacent to the left side posterior teeth with the polyacetal removable partial denture. The lowest stress was seen with the traditional metal framework. Unilateral loads on the right edentulous region produced similar distributed stress under the denture base with all three designs but a somewhat higher intensity with the polyacetal framework. CONCLUSIONS: The polyacetal resin removable partial denture concentrated the highest stresses to the abutment and the bone. The traditional metal framework I-bar removable partial denture most equitably distributed force. The hybrid design that combined a metal framework and polyacetal clasp and denture base may be a viable alternative when aesthetics are of primary concern.

High Frequency Measurements of Viscoelastic Properties of Hydrogels for Vocal Fold Regeneration.

This report describes a torsional wave experiment used to measure the viscoelastic properties of vocal fold tissues and soft materials over the range of phonation frequencies. A thin cylindrical sample is mounted between two hexagonal plates. The assembly is enclosed in an environmental chamber to maintain the temperature and relative humidity at in vivo conditions. The bottom plate is subjected to small oscillations by means of a galvanometer driven by a frequency generator that steps through a sequence of frequencies. At each frequency, measured rotations of the top and bottom plates are used to determine the ratio of the amplitudes of the rotations of the two plates. Comparisons of the frequency dependence of this ratio with that predicted for torsional waves in a linear viscoelastic material allows the storage modulus and the loss angle, in shear, to be calculated by a best-fit procedure. Experimental results are presented for hydrogels that are being examined as potential materials for vocal fold regeneration.

Three-dimensional finite element analysis of the application of attachment for obturator framework in unilateral maxillary defect.

AIMS: The aim of this study was to evaluate the stress on the abutment teeth and framework ina unilateral maxillary defect which was restored by an obturator retained by resin-bonded extra coronal attachment. METHODS: A three-dimensional finite element model of the human unilateral maxillary defect was constructed. Traditional obturator framework with four casting circumferential clasp was established (model 1). A continuous lingual guide plane of 0.5 mm thickness on all of the remaining teeth, with Mini-SG/F attachment on the mesial surface of the central incisor was also established (model 2). The modelling and analytical processes were performed using the ANSYS technologies. RESULTS: Stress was transmitted to the anterior part of the palate, with stress values being lower on the anterior teeth compared with the posteriors. The highest stress value of model 1 and model 2 was 13.1 Mpa, 19.9 Mpa respectively. Stress concentrations were found at the junction of the attachment to the lingual guide plane and the anterior part of the lingual plane. CONCLUSION: The results of this study suggest that the application of a resin-bonded extra coronal attachment for obturator retention is in accordance with the design principles for the restorative treatment of maxillary defects.The design of the attachment framework needs to be further investigated. Benefit can be gained by splinting the abutment teeth.

A molecule carrier.

We found that anthraquinone diffuses along a straight line across a flat, highly symmetric Cu111 surface. It can also reversibly attach one or two CO2 molecules as "cargo" and act as a "molecule carrier," thereby transforming the diffusive behavior of the CO2 molecules from isotropic to linear. Density functional theory calculations indicated a substrate-mediated attraction of approximately 0.12 electron volt (eV). Scanning tunneling microscopy revealed individual steps of the molecular complex on its diffusion pathway, with increases of approximately 0.03 and approximately 0.02 eV in the diffusion barrier upon attachment of the first and second CO2 molecule, respectively.