Disparity in survival benefits of pembrolizumab between Asian and non-Asian patients with advanced cancers: A systematic review and meta-regression analysis.

BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment of malignancies. However, disproportionate enrollment among races and ethnicities places the generalizability of global trial results in doubt. METHODS: In this systematic review, phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers and providing subgroup analyses of Asian and non-Asian participants were included. The primary and secondary effect measures were the mean differences (MDs) in the natural logarithms of the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) between these two subgroups, respectively. We used random-effects meta-analysis to calculate the pooled ratios of HRs (i.e., exp(MD)) and implemented a meta-regression analysis to identify significant covariates. RESULTS: A total of 17 and 11 trials were included in the meta-analyses of OS and PFS, respectively. These trials included 2732 (25.49%) Asian and 7000 (65.32%) non-Asian participants in the OS analysis and 1438 (22.5%) Asian and 4129 (64.61%) non-Asian participants in the PFS analysis. The pooled ratio of HRs for OS was 0.87 (95% CI: 0.76-0.99; p = 0.0391), favoring Asian participants, but no significant difference was found in PFS (pooled ratio of HRs: 0.93; 95% CI: 0.82-1.07; p = 0.2391). Both linear meta-regression analyses revealed an open-label design as a crucial covariate, which indicated more benefits for non-Asian participants. CONCLUSIONS: Compared with non-Asian patients, Asian patients with advanced cancers may derive superior OS benefits from pembrolizumab. Although the results warrant further exploration, this meta-analysis provides insight into clinical research design.

Pressure- and Rate-Dependent Mechanoluminescence with Maximized Efficiency and Tunable Wavelength in ZnS: Mn2+, Eu3.

Mechanoluminescence (ML) has received widespread attention because of potential application in stress sensors and imaging. However, pursuing highly efficient ML remains a challenge due to multifactorial limitations such as pressure and loading rate. Here, we systematically investigate pressure- and rate-dependent ML in Mn2+ and Eu3+ co-doped ZnS in a gigapascal pressure range by using a high-pressure dynamic diamond anvil cell and microsecond time-resolved fluorescent methods and demonstrate the giant tunability in both ML efficiency and wavelength. Compressed from ambient pressure to 11 GPa at different compression rates, ZnS: Mn2+, Eu3+ exhibits a volcano shape in ML emission efficiency with an optimum at ∼3.5 GPa and ∼211.1 GPa/s, at least 1000-fold higher than that measured in the MPa range. The pressure-dependent ML is accompanied with a tunable yellow-to-red emission color change. A combination of high-pressure X-ray diffraction and photoluminescence measurements reveals that the pressure- and rate-dependent ML behavior derives from pressure-induced strengthening of the crystal piezoelectric field and enhanced interaction between the host lattice and doped ions with a significant change of the energy level of the Mn ion. Significantly, the highly efficient ML of ZnS: Mn2+, Eu3+ at the GPa level is reproducible under a compression-decompression process and can be manipulated on a micron scale, implying great potential in mechanical-optical energy conversion and application in dynamic pressure imaging, stress sensors, and multicolor displays.

Maintenance therapy of low-dose nivolumab, S-1, and leucovorin in metastatic pancreatic adenocarcinoma with a germline mutation of MSH6: A case report.

Immune checkpoint inhibitors (ICIs) provide substantial benefits to a small subset of patients with advanced cancer with mismatch repair deficiency (MMRD) or microsatellite instability (MSI), including patients with pancreatic ductal adenocarcinoma (PDAC). However, the long duration of ICI treatment presents a considerable financial burden. We present the case of a 63-year-old woman with metastatic PDAC refractory to conventional chemotherapy. Genetic analyses identified an MSH6 germline mutation and a high tumor mutation burden (TMB). Complete response (CR) was achieved after a short course of low-dose nivolumab (20 mg once every 2 weeks) with chemotherapy. CR was maintained for over 1 year with low-dose nivolumab and de-escalated chemotherapy without any immune-related adverse events. This case supports the further exploration of low-dose, affordable ICI-containing regimens in patients with advanced MSI-high/TMB-high cancer.

Pressure Engineering Promising Transparent Oxides with Large Conductivity Enhancement and Strong Thermal Stability.

Transparent conducting oxides (TCO) with high electrical conductivity and high visible light transparency are desired for a wide range of high-impact engineering. Yet, usually, a compromise must be made between conductivity and transparency, limiting the practical application of a TCO to the next level. Furthermore, TCO performance is highly sensitive to composition, so conventional synthesis methods, such as chemical doping, cannot unravel the mysteries of the quantitative structure-performance relationship. Thus, improving the fundamental understanding or creating materials-by-design has limited success. Here, a strategy is proposed to modulate the lattice and electronic and optical properties precisely by applying pressure on a TCO. Strikingly, after compression-decompression treatment on the indium titanium oxides (ITiO), a highly transparent and metastable phase with two orders of magnitude enhancement in conductivity is synthesized from an irreversible phase transition. Moreover, this phase possesses previously unattainable filter efficiency on hazardous blue light up to 600 °C, providing potential for healthcare-related applications with strong thermal stability up to 200 °C. These results demonstrate that pressure engineering is a clean and effective tool for tailoring functional materials that are not achievable by other means, providing an exciting alternative property-tuning dimension in materials science.

Synthesis of Two-Dimensional CsPb2X5 (X = Br and I) with a Stable Structure and Tunable Bandgap by CsPbX3 Phase Separation.

Perovskite-related materials with various dimensionalities have attracted sustained attention owing to their extraordinary electronic and optoelectronic properties, but it is still challenging in the synthesis of compounds with desired compositions and structures. Herein, a two-dimensional (2D) CsPb2I5 perovskite has been synthesized by the conversion of CsPbI3 at high-pressure and high-temperature (high P-T) conditions, which is quenchable at ambient conditions. In situ synchrotron X-ray diffraction shows that high-pressure monoclinic CsPbI3 converts into tetragonal CsPb2I5 and cubic CsI at 8.7 GPa upon heating from 644 to 666 K. Keeping the tetragonal structure stable, CsPb2I5 exhibits tunable optical properties with the bandgap changing from ∼2.4 eV at ambient pressure to ∼1.4 eV at 36.9 GPa. Further experiments demonstrate similar structural evolution in the typical three-dimensional CsPbBr3 perovskite into 2D CsPb2Br5 at high P-T conditions, indicating that the conversion of CsPbX3 (X = Br and I) into CsPb2X5 is ubiquitous.

Trace holmium assisting delaminated OMS-2 catalysts for total toluene oxidation at low temperature.

In this study, octahedral molecular sieve (OMS-2) is successfully delaminated by using trace holmium (Ho) via a facile redox co-precipitation route, which exhibits high performance for the total toluene oxidation at low temperature. High resolution transmission electron microscope (HRTEM), X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR) analyses verify that abundant multi-phase interfaces and lattice dislocations are formed on the obtained delaminated OMS-2 by the Ho (Ho-OMS-2), which can induce more active oxygen species. In particular, the delaminated OMS-2 with a trace Ho amount has a high Oads/Olatt ratio with a balanced ratio of Mn3+ and Mn4+, demonstrating much higher activity (T100% of 228 °C even under 5 vol% H2O vapor over 0.5% Ho-OMS-2) than the parent OMS-2 (T100% of 261 °C) for the total toluene oxidation. Furthermore, the positive effect of the introduction of H2O on catalytic activity, especially the enhancement of the conversion of intermediates into CO2 and H2O, is verified by the in situ diffuse reflection infrared Fourier transform spectroscopy (DRIFTS). Based on these results, the reaction mechanism for toluene oxidation over the OMS-2 based catalyst is proposed. It is expected to provide an effective preparation method to obtain high-performance catalysts for the VOCs oxidation at low temperatures.

Development of Non-invasive Endoscope System with Magnetic Anchored Ablation Electrode for Early Cancer of Digestive Tract / 中国医疗器械杂志

This study introduces a non-invasive gastrointestinal early cancer magnetic anchor ablation electrode endoscopy system, including a magnetic anchor module and ablation electrode module. The magnetic anchoring module is composed of an external guide magnet and an internal magnet, made of permanent magnet material NdFeB; the ablation electrode module is based on the modification of the front end lens hood of the existing endoscope (CMD-90D LED electronic upper gastrointestinal endoscope). The new endoscope system not only includes all the functions of the original endoscope, but also introduces magnetic anchoring to enable the ablation electrode to be accurately positioned and controllable in the process of treating tumors, avoiding the phenomenon of gastric perforation; the introduction of steep pulse electric field ablation electrodes realizes the purpose of non-invasive treatment. Its clinical application will become a new method to treat early cancer of the digestive tract.

Recent advances in paper-based preconcentrators by utilizing ion concentration polarization.

One of the most cited limitations of biochemical detection is its poor sensitivity, owing to the relatively high complexity of micro-samples. Moreover, some samples cannot be easily self-replicated and their abundance cannot be increased through traditional technologies. Therefore, the preconcentration of low-abundance samples is a key requirement for microfluidic biological analysis. In recent years, the ion-concentration polarization phenomenon has aroused widespread interest in the application of microfluidic technology. In addition, paper-based materials are readily available, easy to modify, and exhibit good hydrophilicity. The study of the ion-concentration polarization preconcentration of micro-samples in paper-based microfluidic chips is of considerable significance. In this review, we discuss the development and applications of ion-concentration polarization paper-based preconcentrator in the past 5 years, with emphasis on key progresses in chip fabrication and performance optimization under different conditions. The current needs and development prospects in this field have also been discussed.

Research progress of magnetic anchor assist technology in surgery / 国际生物医学工程杂志

With the development of magnetic materials more widely used in surgical instruments, the development of magnetic surgery technology has continuously made breakthroughs and innovations. Magnetic anchor assist technology has become an important surgical method due to its precise positioning and non-contact traction. The majority of clinical magnetic anchor system consist a target magnet in vivo and a traction magnet in vitro. The non-contact traction and anchoring of the target can be achieved through the mechanical interaction of the anchor magnet and the traction magnet. This method not only can prevent the entanglement and collision between surgical instruments, but also can provide a good surgical field of vision for the surgical area, making the surgical process safer and more efficient. In this paper, 69 articles related to the application of magnetic anchor assist technology in surgical procedures were retrieved by conducting searches in the Chinese Journal Full-text Database(CNKI), Wanfang Database, VIP Chinese Sci-tech Journal Database, PubMed and other databases. After analysis and evaluation, a total of 36 papers were screened. The research progress and application status of magnetic anchor assist technology in combination with laparoscopy, thoracoscopy, and endoscopy in surgical operations were introduced. The results show that the magnetic anchor assist technology can greatly promote the development of minimally invasive surgery, but there are still problems in the application process, such as mutual interference of magnets and instability of the magnetic force, which still need to be further studied and improved.

The Effect of Bisphosphonates on Managing Osteoporosis After Spinal Cord Injury: A Meta-Analysis.

BACKGROUND: The increased bone loss after spinal cord injury (SCI) is associated with an increase in the morbidity and mortality of fragility fractures, which can constitute a substantial cost to health care systems. Bisphosphonates (BPs) are now the principal class of medications used for osteoporosis. OBJECTIVE: To demonstrate the effect of BPs on treating osteoporosis after SCI. METHODS: A comprehensive search in PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for randomized controlled trials (RCTs), exploring the effect of BPs on osteoporosis after SCI. The primary outcome measures were the BMD of different locations, serum bone turnover marker levels, serum biochemistry marker levels and adverse effect (AE) risks. The final search was performed in September 2019. Reporting was carried out according to PRISMA Guidelines. RESULTS: Six RCTs were included. A total of 147 patients met the inclusion criteria. BPs were found to statistically prevent bone loss in the total hip, femoral neck and trochanter at the 6- and 12-month follow-up points and to increase the BMD of the lumbar spine at the 12-month follow-up time point. BPs had no clear effect on serum PINP or serum calcium levels at the 12-month follow-up time point. CONCLUSION: BP therapy may prevent bone loss in the lumbar spine and hip when administered early after SCI and has relatively high safety.

Research progress of electromagnetic therapy in clinical treatment of common diseases / 国际生物医学工程杂志

As a physical method, electromagnetic therapy has been widely used in clinical treatment of various human diseases. In this paper, a total of 123 research papers related to the clinical application of electromagnetic therapy were retrieved from the Chinese Journal Full-text Database also known as China National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Science and Technology Journal Database (CSTJ), PubMed, Europe PMC, etc. All papers were analyzed and evaluated, and 58 effective articles were selected. The clinical application and therapeutic effects of electromagnetic therapy on several diseases were reviewed, including hypertension, diabetes, insomnia, depression and osteoporosis. The categories of commonly used electromagnetic therapy were sorted out and summarized, including magnetization at acupoints, pulsed electromagnetic fields, gyromagnetic, repetitive transcranial magnetic stimulation, and wearing magnetic items. The results show that electromagnetic therapy has a wide range of applications and small side effects, it has significant effects on some medical diseases, neurological diseases, and orthopedic diseases.

Danshen: a phytochemical and pharmacological overview / 中国天然药物

Danshen, the dried root or rhizome of Salvia miltiorrhiza Bge., is a traditional and folk medicine in Asian countries, especially in China and Japan. In this review, we summarized the recent researches of Danshen in traditional uses and preparations, chemical constituents, pharmacological activities and side effects. A total of 201 compounds from Danshen have been reported, including lipophilic diterpenoids, water-soluble phenolic acids, and other constituents, which have showed various pharmacological activities, such as anti-inflammation, anti-oxidation, anti-tumor, anti-atherogenesis, and anti-diabetes. This article intends to provide novel insight information for further development of Danshen, which could be of great value to its improvement of utilization.

The effects of El Niño-Southern Oscillation events on intertidal seagrass beds over a long-term timescale.

El Niño-Southern Oscillation (ENSO) events can cause dramatic changes in marine communities. However, we know little as to how ENSO events affect tropical seagrass beds over decadal timescales. Therefore, a diverse array of seagrass (Thalassia hemprichii) habitat types were surveyed once every 3 months for 16 years (January 2001 to February 2017) in a tropical intertidal zone that is regularly affected by both ENSO events and anthropogenic nutrient enrichment. La Niña and El Niño events had distinct effects on the biomass and growth of T. hemprichii. During La Niña years, higher (a) precipitation levels and (b) seawater nitrogen concentrations led to increases in seagrass leaf productivity, canopy height, and biomass. However, the latter simultaneously stimulated the growth of periphyton on seagrass leaves; this led to decreases in seagrass cover and shoot density. More frequent La Niña events could, then, eventually lead to either a decline in intertidal seagrass beds or a shift to another, less drought-resistant seagrass species in those regions already characterized by eutrophication due to local anthropogenic activity.

Rapid screening and identification of sesquiterpene lactones in Kudiezi injection based on high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry / 中国天然药物

Sesquiterpene lactones are considered as the major active compounds in Kudiezi injection in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of sesquiterpene lactones in Kudiezi injection using high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. First, two sesquiterpene lactone reference standards were analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Second, based on extracted ion chromatography (EIC) data-mining method and characteristic fragmentation pathways analysis, sesquiterpene lactones in Kudiezi injection were rapidly screened and identified. Finally, an important parameter Clog P was adopted to discriminate the isomers of sesquiterpene lactones. As a result, 50 sesquiterpene lactones were characterized, including 9 sesquiterpene lactone aglycones, 39 sesquiterpene lactone glycosides, and 2 amino acid-sesquiterpene lactone conjugates. Among them, 13 compounds were tentatively identified as new compounds. The results demonstrated that the established method would be a rapid, effective analytical tool for screening and identification of sesquiterpene lactones in the complex system of natural medicines.

Metabolites of tanshinone Ⅰ and tanshinone ⅡA in rats / 中国中药杂志

An efficient method of ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap (UHPLC-LTQ-Orbitrap) mass spectrometer was established to elucidate the metabolites of tanshinone Ⅰ and tanshinone ⅡA in rats. Urine and plasma samples were collected after oral gavage. After processing biological sample by solid phase extraction, Waters ACQUITY HPLC BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) was used with 0.1% formic acid (A) - acetonitrile (B) solution as the mobile phase for gradient elution. The plasma, urine and the blank samples were then analyzed by ESI-LTQ-Orbitrap equipped with an ESI ion source under positive ion mode. On the basis of the accurate mass measurements, multiple mass spectra and comparison of data with published literature, a total of 26 metabolites were tentatively identified and characterized in the rat samples. Among them, 7 metabolites were derived from tanshinone Ⅰ through metabolic pathways of glucuronide conjugation, hydroxylation, reduction reaction, demethylation reaction, methylation, sulfate conjugation and their composite reactions. Nineteen metabolites were derived from tanshinone ⅡA through metabolic pathways of hydroxylation, reduction reaction, methylation, sulfate conjugation, glucuronidation, glucosylation and their complicated reactions. The results showed that the metabolism of tanshinone Ⅰ and tanshinone ⅡA in rats could be comprehensively clarified by using UHPLC-LTQ-Orbitrap mass spectrometer, providing material basis for the further research in terms of pharmacodynamics, toxicology, and secondary development of Chinese medicine.

Identification of metabolites of Danshensu in rats / 中国中药杂志

To identify the metabolites of Danshensu in plasma and urine in rats by using UHPLC-LTQ-Orbitrap method. After oral gavage of Danshensu CMC-Na suspension in SD rats, urine and plasma samples were collected and processed by solid phase extraction. ACQUITY UPLC BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) was utilized, with 0.1% formic acid (A)-acetonitrile (B) solution as the mobile phase for gradient elution. Negative electrospray ion mode based data-acquisition method was established to collect the mass spectrometry data of biological samples. As a result, Danshensu and 21 Danshensu Ⅰ phase and Ⅱ phase metabolites were finally identified according to the accurate mass measurements, mass fragmentation behaviors and comparing with the reference standards. The main metabolic pathways included dehydration, methylation, glucuronide conjugation, sulfate conjugation and their composite reactions. Consequently, our study expounded metabolites of Danshensu in rats based on UHPLC-LTQ-Orbitrap method and provided a reference for further researches on therapeutic material basis and mechanism of Danshensu.

Rapid screening and identification of sesquiterpene lactones in Kudiezi injection based on high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry / 中国天然药物

Sesquiterpene lactones are considered as the major active compounds in Kudiezi injection in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of sesquiterpene lactones in Kudiezi injection using high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. First, two sesquiterpene lactone reference standards were analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Second, based on extracted ion chromatography (EIC) data-mining method and characteristic fragmentation pathways analysis, sesquiterpene lactones in Kudiezi injection were rapidly screened and identified. Finally, an important parameter Clog P was adopted to discriminate the isomers of sesquiterpene lactones. As a result, 50 sesquiterpene lactones were characterized, including 9 sesquiterpene lactone aglycones, 39 sesquiterpene lactone glycosides, and 2 amino acid-sesquiterpene lactone conjugates. Among them, 13 compounds were tentatively identified as new compounds. The results demonstrated that the established method would be a rapid, effective analytical tool for screening and identification of sesquiterpene lactones in the complex system of natural medicines.

Preparation of Melamine Molecularly Imprinted Surface Plasmon Resonance Sensor and Its Analytical Application / 分析化学

The melamine molecular imprinted polymer ( MIP ) membrane immobiliZed on the surface of the surface plasmon resonance ( SPR) chip was prepared with allylcyanurate and ethylene glycol dimethacrylate as a functional monomer and cross-linker, respectively.Based on the ratio of the intercept to the slope of Langmuir equation for imprinted polymer, the association constant ( Kass ) of imprinted sites in the imprinted film to melamine was calculated to be 1.40 × 108 L/mol.The SPR sensor showed high selectivity to the template molecule melamine, and the best response was obtained at pH=7.5.The method showed good linearity in the melamine concentration range of 0.1-10.0 nmol/L ( R=0.9991 ).Based on a signal to noise ratio of 3, the detection limits of melamine were 62.6 pmol/L and 56.4 pmol/L for the milk and milk powder, respectively.The recoveries were 91.5% for milk and 92.0% for milk powder.These results suggest that SPR sensing combined with MIP film is a promising alternative method for detection of melamine.

Hardware System for the Test of Artificial Joint Biomechanics / 中国医疗器械杂志

In the research of artificial joint biomechanics, it is a common method in the world to evaluate the biomechanical properties of the implanted fixtures through experiments . The domestic research started late, and the corresponding testing methods were lacking. There is still no unified standard. In this paper, a complete hardware test system was designed and built around the existing mechanical testing machine, including:binocular vision catcher, torque bearing clamp, film pressure sensor and so on. The system can accurately measure the relative motion angle value, external torque value, and inter pressure value of each joint. It has some reference significance for the forming and standardization of the artificial joints' evaluation system.

Development of Software System for Artificial Joint Biomechanics / 中国医疗器械杂志

In the research of artificial joint biomechanics, it is a common method in the world to evaluate the biomechanical properties of the implanted fixtures through experiments . The domestic research started late, and the corresponding testing software were lacking. There is still no special software. In this paper, an integrated software test system was designed and built based on the existing hardware system, including:hardware control, data collection, data save, data processing and display. It can directly show the 3D motion trajectory and the angle curve of joints. The system can accurately measure the relative motion angle value, external torque value, and inter pressure value of each joint. It has some reference significance for the development of the artificial joints' evaluation system.