A novel tricyclic BTK inhibitor suppresses B cell responses and osteoclastic bone erosion in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by joint leukocyte infiltration, synovial inflammation and bone damage result from osteoclastogenesis. Bruton's tyrosine kinase (BTK) is a key regulator of B cell receptor (BCR) and Fc gamma receptor (FcγR) signaling involved in the pathobiology of RA and other autoimmune disorders. SOMCL-17-016 is a potent and selective tricyclic BTK inhibitor, structurally distinct from other known BTK inhibitors. In present study we investigated the therapeutic efficacy of SOMCL-17-016 in a mouse collagen-induced arthritis (CIA) model and underlying mechanisms. CIA mice were administered SOMCL-17-016 (6.25, 12.5, 25 mg·kg-1·d-1, ig), or ibrutinib (25 mg·kg-1·d-1, ig) or acalabrutinib (25 mg·kg-1·d-1, ig) for 15 days. We showed that oral administration of SOMCL-17-016 dose-dependently ameliorated arthritis severity and bone damage in CIA mice; it displayed a higher in vivo efficacy than ibrutinib and acalabrutinib at the corresponding dosage. We found that SOMCL-17-016 administration dose-dependently inhibited anti-IgM-induced proliferation and activation of B cells from CIA mice, and significantly decreased anti-IgM/anti-CD40-stimulated RANKL expression in memory B cells from RA patients. In RANKL/M-CSF-stimulated RAW264.7 cells, SOMCL-17-016 prevented osteoclast differentiation and abolished RANK-BTK-PLCγ2-NFATc1 signaling. In summary, this study demonstrates that SOMCL-17-016 presents distinguished therapeutic effects in the CIA model. SOMCL-17-016 exerts a dual inhibition of B cell function and osteoclastogenesis, suggesting that it to be a promising drug candidate for RA treatment.

Research progress of bacterial minimal genome.

Bacteria with the smallest genome contain genes necessary for self-sustaining replication only, giving the organisms advantages to serve as a potential industrial production platform. Many strains with reduced genomes have been constructed, owing to the development of high-throughput DNA sequencing and synthesis technology. This review first describes the concept of minimal genomes, summarizes the relevant research progress of bacterial essential genes, then systematically lists the work related to artificial reduction and synthesis of bacterial genomes, finally discusses the technical obstacles and limitations encountered in the process of designing and constructing reduced genomes, hoping to provide a theoretical basis for the experiment and application of artificially synthesized genomes.

Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein.

Prostate cancer frequently metastasizes to the skeleton but the underlying mechanism remains largely undefined. Discoidin domain receptor 2 (DDR2) is a member of receptor tyrosine kinase (RTK) family and is activated by collagen binding. This study aimed to investigate the function and detailed mechanism of DDR2 in prostate cancer bone dissemination. Herein we found that DDR2 was strongly expressed in bone-metastatic prostate cancer cells and tissues compared to that in normal controls. Enhanced expression of constitutively activated DDR2 led to elevation in motility and invasiveness of prostate cancer cells, whereas knockdown of DDR2 through specific shRNA caused a dramatic repression. Knockdown of DDR2 in prostate cancer cells resulted in significant decrease in the proliferation, differentiation and function of osteoblast. Over-expression of DDR2 in prostate cancer cells resulted in notable acceleration of osteoclast differentiation and bone resorption, whereas knockdown of DDR2 exhibited the opposite effects. An intrabone injection bone metastasis animal model demonstrated that DDR2 promoted osteolytic metastasis in vivo. Molecular evidence demonstrated that DDR2 regulated the expression, secretion, and promoter activity of parathyroid hormone-related protein (PTHrP), via modulating Runx2 phosphorylation and transactivity. DDR2 was responsive to TGF-ß and involved in TGF-ß-mediated osteoclast activation and bone resorption. In addition, DDR2 facilitated prostate cancer cells adhere to type I collagen. This study reveals for the first time that DDR2 plays an essential role in prostate cancer bone metastasis. The mechanism disclosure may provide therapeutic targets for the treatment of prostate cancer.

Computer-Vision Based Gesture-Metasurface Interaction System for Beam Manipulation and Wireless Communication.

Hand gesture plays an important role in many circumstances, which is one of the most common interactive methods in daily life, especially for disabled people. Human-machine interaction is another popular research topic to realize direct and efficient control, making machines intelligent and maneuverable. Here, a special human-machine interaction system is proposed and namedas computer-vision (CV) based gesture-metasurface interaction (GMI) system, which can be used for both direct beam manipulations and real-time wireless communications. The GMI system first needs to select its working mode according to the gesture command to determine whether to perform beam manipulations or wireless communications, and then validate the permission for further operation by recognizing unlocking gesture to ensure security. Both beam manipulation and wireless communication functions are validated experimentally, which show that the GMI system can not only realize real-time switching and remote control of different beams through gesture command, but also communicate with a remote computer in real time by translating the gesture language to text message. The proposed non-contact GMI system has the advantages of good interactivity, high flexibility, and multiple functions, which can find potential applications in community security, gesture-command smart home, barrier-free communications, and so on.

Multichannel highly secure wireless communication system with information camouflage capability.

Information metasurface has shown great potential in wireless communications owing to its ability to flexibly control electromagnetic waves. However, it is still a big challenge to achieve high-security and large-channel capacity wireless communications by a simple system. Here, we propose a space-polarization-division multiplexing secure wireless communication system with information camouflage capability based on the information metasurface, which can realize multichannel encrypted wireless communications with different polarization coding strategies independently and simultaneously. A polarization mask key is introduced to encrypt the target message, and the cipher message is further concealed behind a cover image with steganography and sent to the user by using the polarization modulation strategy. Different polarization mask keys can be adopted in each individual communication by changing the polarization coding strategy to enhance the system security. The proposed scheme integrates computational algorithm encryption and physical layer security together and thus has the advantages of high security, large channel capacity, and strong camouflage ability.

A survey of Kansas beef producers and consumers who participate in business-to-consumer marketing of beef.

Following the coronavirus disease 2019 (COVID-19) pandemic, producer and consumer interest in business-to-consumer (B2C) beef sales increased. The objective of the current study was to assess current B2C beef producer and consumer attitudes and understandings of the B2C beef marketing process in order to identify knowledge gaps and strategies to improve producer/consumer interactions. Both producers and customers of local beef were recruited using a large online platform (https://shopkansasfarms.com), and descriptive statistics were used to summarize the data. In total, 41 B2C beef producers and 174 consumers who had either previously participated in B2C marketing or intended to participate were surveyed. Most producers (69.8%) only produced beef and produced only a small number (1 to 20 head) of animals per year. Many (43.9%) reported selling 100% of beef directly to consumers, while 29.3% reported selling less than 20% through this channel. Almost all (97.3%) of the producers indicated that increased sales directly to consumers would be desirable, with most (87.1%) considering this marketing channel as the most profitable. Marketing beef in smaller portions, including portioned cuts, was popular, reported by more than 62% of producers, while whole carcass sales were lower. Word-of-mouth (91.3%) and social media (65.8%) were the most popular forms of advertisement used by producers and more than one-third of producers (38.9%) reported having trouble with customers regarding a sale. Over 60% of consumers indicated they had purchased B2C beef less than 5 times, with more than 73% indicating that more than 75% of their beef purchased was local. Low take-home weights, portion sizes, and quality were among consumers' most cited troubles. Lack of freezer space (25%), price (24.9%), and quantity of product (41.7%) were reported as the largest barriers to consumer participation in B2C marketing. Both consumers and producers indicated that consumer testimonials would be the most beneficial in improving producer/consumer interactions, with educational materials from government sources viewed as the least beneficial. These results provide a baseline for B2C beef marketing and provide insight into impactful strategies to use to assist in this process.

Capsaicin ameliorates intermittent high glucose-mediated endothelial senescence via the TRPV1/SIRT1 pathway.

BACKGROUND: Patients with diabetes have accelerated vascular aging when compared with healthy individuals. Hyperglycemia, especially intermittent high glucose (IHG), is the main cause of vascular endothelial senescence. Capsaicin, a major component of chili pepper is thought to contribute to cardiovascular protection by spicy food. OBJECTIVE: To investigate the pathway related with the effects of capsaicin on endothelial cell senescence induced by IHG. METHODS: HUVECs were exposed to IHG (5 mM or 33 mM glucose, alternating every 12 hours for 3 days) and treated with capsaicin at 0.3, 1 and 3 µM. To determine endothelial cell senescence, we examined the senescence-related ß-galactosidase staining, cell cycle arrest, cell viability, as well as production of reactive oxygen species (ROS). To evaluate the involvement of TRPV1/[Ca2+]i/CaMKII/AMPK/SIRT1 pathway in anti- senescence effects of capsaicin, HUVECs were treated with CAPZ (a TRPV1 antagonist), BAPTA-AM (an intracellular calcium chelator), KN62 (a CaMKII antagonist), compound C (an AMPK inhibitor), or EX527 (a SIRT1 inhibitor). To knockdown TRPV1, HUVECs were transfected with shRNA lentivirus targeting TRPV1. The levels of SIRT1, p21, TRPV1, AMPK and phospho-AMPK were evaluated by western blotting. RESULTS: IHG suppressed the levels of SIRT1 and enhanced endothelial senescence. Capsaicin upregulated SIRT1 expression and downregulated the senescence marker, p21, thereby protecting endothelial cells from IHG-induced senescence as indicated by relieved G0/G1 phase arrest, improved cell viabilities, and reduced counts of senescent cells and ROS production. Pre-treatment with CAPZ, BAPTA-AM, KN62 or compound C abrogated the anti-senescence effects of capsaicin. Capsaicin restored AMPK phosphorylation and IHG-inhibited TRPV1 expression. Moreover, TRPV1 silencing suppressed SIRT1 expression and abolished the anti-senescence effects of capsaicin. CONCLUSION: Capsaicin elevates SIRT1 levels through TRPV1/[Ca2+]i/CaMKII/AMPK pathway and suppresses IHG-mediated endothelial cell senescence. This study provides initial evidence that capsaicin is a potential candidate for the prevention of vascular aging in diabetes.

Combination of hyaluronic acid hydrogel scaffold and PLGA microspheres for supporting survival of neural stem cells.

PURPOSE: To develop a biomaterial composite for promoting proliferation and migration of neural stem cells (NSCs), as well as angiogenesis on the materials, to rescue central nervous system (CNS) injuries. METHODS: A delivery system was constructed based on cross-linked hyaluronic acid (HA) hydrogels, containing embedded BDNF and VEGF-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery and support for NSCs in the CNS. The surface morphologies were evaluated by SEM and AFM, mechanical property was investigated by rheological tests, and release kinetics were performed by ELISA. Bioactivity of released BDNF and VEGF was assessed by neuron and endothelial cell culture, respectively. Compatibility with NSCs was studied by immunofluorescent staining. RESULTS: Release kinetics showed the delivery of BDNF and VEGF from PLGA microspheres and HA hydrogel composite were sustainable and stable, releasing ~20-30% within 150 h. The bioactivities preserved well to promote survival and growth of the cells. Evaluation of structure and mechanical properties showed the hydrogel composite possessed an elastic scaffold structure. Biocompatibility assay showed NSCs adhered and proliferated well on the hydrogel. CONCLUSIONS: Our created HA hydrogel/PLGA microsphere systems have a good potential for controlled delivery of varied biofactors and supporting NSCs for brain repair and implantation.

[Community Characteristics of Methanogens and Methanogenic Pathways in Salt-tolerant Rice Soil].

It is known that methanogens play a critical role in the carbon cycle in soil, while methanogen community characteristics and their environmental influencing factors in the soil planted with salt-tolerant rice remain unclear. In this study, methanogen abundance, community composition, and relationships with environmental factors in soils planted with the salt-tolerant rice (YC1703) and ordinary rice (Lindao 10) were evaluated in the rice improvement demonstration base of Qingdao Wisdom Agricultural Industry using real-time fluorescence quantitative PCR and Illumina high-throughput sequencing. The results indicated that the abundance and community richness of methanogens in Lindao 10 soil were significantly higher than those in YC1703 soil, and methanogens in YC1703 soil exhibited higher diversity. The combined effects of rice varieties, rice growth period, and environmental factors had impacts on the methanogen community. The hydrogenotrophic methanogens were dominant in the YC1703 and Lindao 10 soils; thus, we speculated that the dominant pathway of methane production in these soils was hydrogenotrophic methanogenesis.

Long-term outcomes of delayed percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: A propensity score-matched retrospective study.

ABSTRACT: The best time window of percutaneous coronary intervention (PCI) is within 12 hours for ST-segment elevation myocardial infarction (STEMI). However, there is limited evidence about the proper time of PCI for delayed STEMI patients.From June 2014 to June 2015, a total of 268 patients receiving PCI with second-generation drug-eluting stent in a Chinese hospital after 3 days of STEMI onset were enrolled in this retrospective study, who were divided into the early group (3-14 days) and the late group (>14 days). A propensity score match was conducted to reduce the baseline difference. The primary endpoint of all-cause death and secondary endpoints of major adverse cardiac and cerebrovascular event (myocardial infarction [MI], stroke, emergent revascularization, and rehospitalization due to heart failure) were compared using survival analysis.At last, 182 cases were matched after propensity score match, with no statistical difference in baseline characteristics and PCI data. Kaplan-Meier survival curve demonstrated no difference in all-cause death of the 2 groups (P = .512). However, the early group presented a higher incidence of MI than the late group (P = .036). The multivariate Cox regression analysis also demonstrated that the early PCI was an independent risk factor for MI compared with late PCI (hazard ratio = 3.83, 95%CI [1.91-8.82], P = .001). There was no statistical difference in other major adverse cardiac and cerebrovascular event, including stroke, emergent revascularization, and rehospitalization due to heart failure.Using the 2nd drug-eluting stent, early PCI (3-14 days) and late PCI (>14 days) have comparable efficacy and outcomes. However, patients receiving early PCI are subjected to a relatively higher risk of recurrent MI.

Anti-nociceptive, anti-inflammatory and anti-arthritic activities of pregnane glycosides from the root bark of Periploca sepium Bunge.

ETHNOPHARMACOLOGICAL RELEVANCE: Periploca sepium Bunge (P. sepium) is used in traditional Chinese medicine (TCM) for the treatment of autoimmune diseases, particularly rheumatoid arthritis. Periploca sepium periplosides (PePs), isolated from the root bark of P. sepium, characterized as the cardiac glycosides-free pregnane glycosides fraction, is expected to possess therapeutic potential on inflammatory arthritis. AIM OF THE STUDY: The current study is designed to evaluate the anti-nociceptive, anti-inflammatory and anti-arthritic activities effects of the PePs. MATERIALS AND METHODS: The anti-nociceptive activity of PePs was examined in the writhing test and hot-plate test in mice. The anti-inflammatory activity of PePs was determined by the 2, 4-dinitro-1-fluorobenzene (DNFB)-induced ear edema model and the carrageenan induced paw edema model in mice. The anti-arthritic activity of PePs was investigated by evaluating the joint inflammation and arthritis pathology in rat adjuvant induced arthritis (AIA) and murine collagen induced arthritis (CIA). Phytohaemagglutinin M (PHA-M) -elicited human peripheral blood mononuclear cells (PBMCs) were further applied to assess the suppressive activity of PePs on IFN-γ and IL-17 production. RESULTS: PePs treatment markedly decreased the acetic acid-induced visceral nociceptive response and increased the hot-plate pain threshold. Further, oral administration of PePs exhibited anti-inflammatory activity by decreasing DNFB-induced ear edema in mice and carrageenan-induced paw edema in rats. Moreover, oral treatment of PePs ameliorated joint swelling and attenuated bone erosion in rodent arthritis, and the therapeutic benefits were partially attributed to the suppression of proinflammatory cytokines such IFN-γ and IL-17. Moreover, PePs suppressed the proliferation as well as IFN-γ and IL-17 secretion in PHA-M-elicited human PBMCs in a concentration dependent manner. CONCLUSIONS: Taken together, our results justified the traditional use of Periploca sepium Bunge for the treatment of diseases associated with inflammation and pain.

Real-World Analysis of the Curative Effect in Patients with Proliferative Diabetic Retinopathy of Different Traditional Chinese Medicine Syndrome Types Treated by Anti-vascular Endothelial Growth Factor Combined with Pars Plana Vitrectomy / 广州中医药大学学报

Objective To compare the clinical efficacy of anti-vascular endothelial growth factor(VEGF)combined with pars plana vitrectomy(PPV)treatment for patients with proliferative diabetic retinopathy(PDR)of different traditional Chinese medicine(TCM)syndrome types in the real world.Methods A prospective real-world study was performed in the 36 patients(involving 42 eyes)with PDR treated by anti-VEGF combined with PPV in the Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2019 to December 2019.According to the TCM syndrome manifestations,the patients were differentiated as qi-yin deficiency complicated with blood stasis obstructing collaterals type(15 cases,involving 18 eyes;shorten as qi-yin deficiency type),liver-kidney deficiency and ocular collaterals failing in the nourishment type(14 cases,involving 17 eyes;shorten as liver-kidney deficiency type),and yin-yang deficiency complicated with blood stasis and phlegm coagulation type(7 cases,involving 7 eyes;shorten as yin-yang deficiency type).The patients were treated with anti-VEGF therapy first and then received PPV after 5-7 days.Aqueous humor was sampled during anti-VEGF therapy and PPV.After treatment,the efficacy of PDR patients with different TCM syndromes was compared.Moreover,the patients were observed in the best corrected visual acuity(BCVA)of the affected eyes before surgery and 3 months after surgery,levels of cytokines in the aqueous humor before and after anti-VEGF treatment,macular central retinal thickness(CRT),area of the foveal avascular zone(FAZ),the blood density of macular center,inner ring,outer ring and intact macula 3 months after surgery,and the postoperative complications.Results(1)The difference of the therapeutic efficacy of PDR patients with various TCM syndrome types was statistically significant(P＜0.05).Among 3 syndrome types,the best efficacy was found in the qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type,with the total efficacy rate being 88.89%(16/18),52.94%(9/17),and 42.86%(3/7),respectively.(2)Three months after surgery,the logarithmic value of minimum angle of resolution(LogMAR)for BCVA of patients with qi-yin deficiency type was significantly superior to that of patients with yin-yang deficiency type,with the difference being statistically significant(P＜0.05).After the anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients varied in the 3 syndrome types:vascular endothelial growth factor A(VEGF-A)level in the patients with the 3 syndrome types was significantly lower,placental growth factor(PLGF)and angiopoietin-like protein 4(ANGPTL4)levels in the patients with qi-yin deficiency type were higher,and interleukin 8(IL-8)level in the patients with liver-kidney deficiency type was higher than those before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The blood density of macular outer ring and intact macula in the patients with qi-yin deficiency type and liver-kidney deficiency type was larger than that in the patients with yin-yang deficiency type,and the differences were statistically significant(P＜0.05).However,the differences of CRT,FAZ area,and blood density of macular center and inner ring among the 3 syndrome types were not statistically significant(P＞0.05).(3)The incidence of postoperative complications in the patients with yin-yang deficiency type was relatively high,but the difference among the 3 syndrome types was not statistically significant(P＞0.05).Conclusion In the real world,the best efficacy of anti-VEGF combined with PPV treatment in PDR patients with different TCM syndrome types can be achieved in the patients differentiated as qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type.After anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients vary in the 3 syndrome types.Three months after the operation,the patients with qi-yin deficiency type and liver-kidney deficiency type have larger blood density of macular outer ring and intact macula,and exert good prognosis.

Sonogenetics and its application in military medicine / 解放军医学杂志

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

Implantation of neural stem cells embedded in hyaluronic acid and collagen composite conduit promotes regeneration in a rabbit facial nerve injury model.

The implantation of neural stem cells (NSCs) in artificial scaffolds for peripheral nerve injuries draws much attention. NSCs were ex-vivo expanded in hyaluronic acid (HA)-collagen composite with neurotrophin-3, and BrdU-labeled NSCs conduit was implanted onto the ends of the transected facial nerve of rabbits. Electromyography demonstrated a progressive decrease of current threshold and increase of voltage amplitude in de-innervated rabbits after implantation for one, four, eight and 12 weeks compared to readouts derived from animals prior to nerve transection. The most remarkable improvement, observed using Electrophysiology, was of de-innervated rabbits implanted with NSCs conduit as opposed to de-innervated counterparts with and without the implantation of HA-collagen, NSCs and HA-collagen, and HA-collagen and neurotrophin-3. Histological examination displayed no nerve fiber in tissue sections of de-innervated rabbits. The arrangement and S-100 immunoreactivity of nerve fibers in the tissue sections of normal rabbits and injured rabbits after implantation of NSCs scaffold for 12 weeks were similar, whereas disorderly arranged minifascicles of various sizes were noted in the other three arms. BrdU+ cells were detected at 12 weeks post-implantation. Data suggested that NSCs embedded in HA-collagen biomaterial could facilitate re-innervations of damaged facial nerve and the artificial conduit of NSCs might offer a potential treatment modality to peripheral nerve injuries.

Meta-analysis of Effect on Magnesium Sulfate as Adjunctive Therapy for Severe Acute Pancreatitis / 医学研究杂志

Objective To systematically evaluate the efficacy of magnesium sulfate combined with conventional treatment in the treatment of severe acute pancreatitis(SAP).Methods Randomized controlled trial(RCT)comparing the efficacy difference between conventional treatment and conventional treatment combined with magnesium sulfate in the treatment of SAP were included by searching PubMed,Web of Science,CNKI and WanFang data knowledge service platform from the establishment of the database to July 1,2022.Meta-analysis was performed by Review Manager 5.4software to evaluate the prognosis of patients.Results Compared with the conven-tional treatment(water fasting,gastrointestinal decompression,fluid replacement,antibiotic treatment,inhibition of pancreatic enzyme se-cretion,maintenance of water,electrolyte and acid-base balance),magnesium sulfate combined with conventional treatment can reduce the mortality and complications related to SAP,and shorten the length of hospital stay,relief time of abdominal pain,duration of fever.Conclusion Magnesium sulfate combined with conventional treatment is superior to conventional treatment in improving the mortality,complication rate,length of hospital stay,relief time of abdominal pain,duration of fever in patients with SAP.

Changes of Macular Microcirculation After Near Work in Myopic Patients / 中山大学学报(医学科学版)

ObjectiveTo compare the changes of retinal microcirculation indexes in the anterior and posterior macular areas of the eyes used at close range and to explore the possible causes of myopia affected by near work. MethodsWatching mobile phone video for 1 hour at close range was used as the method of defining near work. The OCTA technology was used to measure the superficial retinal microcirculation indexes within 6 by 6 mm macular area before and after near work， including the superficial retinal VLD from the nerve fiber layer to the inner boundary of the outer plexiform layer， the VPD， nonperfusion area of FAZ， FAZ-P and FAZ circulation，. The FAZ was divided int center， inner layer， outer layer and overall according to the region， and 11 microcirculation indexes were obtained to compare the differences between before and after near work. ResultsThe indexes of superficial retinal microcirculation in the macular area generally decreased after near work， except for FAZ-A and FAZ-P（P = 0.148， 0.975）. The largest differences among both VLD and VPD occurred between the central and inner layer（Difference = 1.00， 0.80， 0.02， 0.02，P = 0.001， 0.008， 0.001， 0.008）. No differences in microcirculation indexs were observed in the macular area after near work with different diopters and axial lengths. ConclusionNear work may affect the occurrence and development of myopia by affecting the changes of retinal microcirculation in the superficial layer of macula， leading to ischemia and hypoxia.

Prognostic stratification of baseline PET metabolic parameters combined with Bcl-2/c-Myc dual expression in patients with primary gastrointestinal diffuse large B-cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore whether baseline PET metabolic parameters combined with B-cell lymphoma-2 (Bcl-2)/cellular-myelocytomatosis viral oncogene (c-Myc) dual expression (DE) can improve the prognostic stratification of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).Methods:From March 2011 to November 2019, 74 patients (33 males, 41 females; age: 20-87 years) pathologically diagnosed with PGI-DLBCL prior to treatment in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and the First Affiliated Hospital of Nanjing Medical University were retrospectively included. Baseline PET/CT scans were calculated automatically using the boundaries of voxels presenting a SUV max≥2.5, and metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were determined. Expressions of Bcl-2 and c-Myc were detected at protein levels by immunohistochemistry (IHC). A predicting model comprised of MTV and DE was constructed and patients were divided into 3 groups, including low-risk group (low MTV and non-DE), mediate-risk group (high MTV or DE) and high-risk group (high MTV and DE). The distributions of progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results:Of 74 patients, 20 relapsed or progressed, 13 died, and 29.7%(22/74) patients were DE positive. Multivariate analysis revealed that MTV (hazard ratio ( HR)=9.110, 95% CI: 1.429-18.615, P=0.012) and DE ( HR=9.837, 95% CI: 1.690-57.260, P=0.011) were independent predictors of PFS, while MTV ( HR=12.470, 95% CI: 3.356-46.336, P<0.001) was the only independent predictor of OS. In the predicting model for PFS, low-risk group ( n=42) and mediate-risk group ( n=20) exhibited significant difference ( χ2=7.84, P=0.005), and mediate-risk group and high-risk group ( n=12) also exhibited significant difference ( χ2=18.72, P<0.001). Conclusions:MTV and DE can independently predict PFS of patients with PGI-DLBCL, and MTV can independently predict OS. The predicting model for PFS combining MTV with DE may further improve the ability of clinicians to stratify patients in terms of differential prognoses.

Textual research classic decoction Danggui Yinzi by ancient and modern literatures / 国际中医中药杂志

The Danggui Yinzi, as one of the classic prescriptions, was first recorded in Yan's Jisheng Prescription and is mainly used to treat various skin diseases with blood deficiency and wind dryness. By referring to ancient books and modern literature researches, this study analyzed and summarized the literature of Danggui Yinzi from the aspects of prescription origin, composition, addition and subtractive changes of flavor, dosage and decocting and taking method, discrimination of prescription and efficacy, raw material and processing of medicinal materials, and modern clinical application. Textual researches explored more than 80 ancient literature and 170 modern literature and showed its content included Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, Rehmannia Radix, Tribuli Fructus, Saposhnikoviae Radix, Schizonepetae Spica, Polygoni Multiflora Radix, Astragali Radix, Glycyrrhizae Radix et Rhizoma. It was cooked by water. It was used for the patients with skin diseases and Chinese pattern of blood deficiency wind drying. It has showed a wide range of applications, and similar application in ancient and modern time. This paper provides a more comprehensive reference for the research and development of compound preparation of Danggui Yinzi.

Prognostic value of metabolic parameters measured by 18F-FDG PET/CT in patients with primary advanced cutaneous malignant melanoma / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of metabolic parameters measured by 18F-FDG PET/CT in patients with primary advanced cutaneous malignant melanoma (CMM). Methods:A retrospective analysis was comprised of 42 patients with advanced CMM (15 males and 27 females; median age: 60.0 years) from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between June 2014 and December 2019. All patients were initially diagnosed by pathology, and underwent 18F-FDG PET/CT imaging. 18F-FDG PET/CT parameters including SUV max, SUV mean, total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) of metastatic lesions were measured. ROC curve analysis was performed to obtain the optimal cut-off values of those metabolic parameters for predicting progression-free survival (PFS) and over-all survival (OS). Patients were divided into different groups based on their metabolic parameters (≥cut-off values or <cut-off values), and Kaplan-Meier survival curve and log-rank test were used to analyze the OS/PFS differences between 2 groups. The independent prognostic risk factors of PFS and OS were screened by univariate analysis and Cox proportional risk model. Results:The median follow-up time of 42 patients with advanced CMM was 26.3 months, with 32 patients suffered from disease progression and 21 patients died, and the median survival was 33.1 months. The optimal cut-off values for PFS/OS were 4.63/4.77 for SUV max, 3.31/3.31 for SUV mean, 8.22 cm 3/22.32 cm 3 for TMTV, and 18.22 g/51.37 g for TLG, respectively. Kaplan-Meier analysis and log-rank test showed that patients with SUV max ≥4.63 or SUV mean ≥3.31 suffered from poorer PFS ( χ2 values: 7.12, 5.42, P values: 0.008, 0.020), meanwhile, patients with SUV max ≥4.77 or TMTV≥22.32 cm 3 or TLG≥51.37 g suffered from poorer OS ( χ2 value: 4.73, 5.60, 6.31, P values: 0.030, 0.018, 0.012). Multivariate analysis demonstrated that SUV max was significant predictor for both PFS (hazard risk ( HR)=3.03(95% CI: 1.23-7.45), P=0.016) and OS ( HR=3.62(95% CI: 1.19-11.00), P=0.023), while TMTV and TLG were significant predictors for OS ( HR: 2.87(95% CI: 1.20-6.87), 3.34(95% CI: 1.39-8.05); P values: 0.018, 0.007). Conclusions:Baseline 18F-FDG PET/CT metabolic parameters have certain value in prediction of prognosis in patients with advanced CMM. SUV max of metastatic lesions is an independent prognostic risk factor for both PFS and OS, and TMTV and TLG are independent prognostic risk factors for OS in patients with advanced CMM.

Predictive value of multi-parameter model incorporating PET-based radiomics features for survival of older patients(≥60 years) with diffuse large B-cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the prognostic value of 18F-FDG PET-based radiomics features by machine learning in older patients(≥60 years) with diffuse large B-cell lymphoma (DLBCL). Methods:A total of 166 older patients (88 males, 78 females, age: 60-93 years) with DLBCL who underwent pre-therapy 18F-FDG PET/CT from March 2011 to November 2019 were enrolled in the retrospective study. There were 115 patients in training cohort and 51 patients in validation cohort. The lesions in PET images were manually drawn and the obtained radiomics features from patients in training cohort were selected by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (Xgboost), and then classified by support vector machine (SVM) to build radiomics signatures (RS) for predicting overall survival (OS). A multi-parameter model was constructed by using Cox proportional hazard model and assessed by concordance index (C-index). Results:A total of 1 421 PET radiomics features were extracted and 10 features were selected to build RS. The univariate Cox regression analysis showed that RS was a predictor of OS (hazard ratio ( HR)=5.685, 95% CI: 2.955-10.939; P<0.001). The multi-parameter model that incorporated RS, metabolic metrics, and clinical risk factors, exhibited significant prognostic superiority over the clinical model, PET-based model, and the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in terms of OS (training cohort: C-index: 0.752 vs 0.737 vs 0.739 vs 0.688; validation cohort: C-index: 0.845 vs 0.798 vs 0.844 vs 0.775). Conclusions:RS can be used as a survival predictor for older patients(≥60 years) with DLBCL. Furthermore, the multi-parameter model incorporating RS is able to successfully predict prognosis.