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Background Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. Results Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. Conclusions The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. Graphic abstract

Background Osteoporosis is a major public health concern for the elderly population and is characterized by fatigue load resulting in bone microdamage. The ability of bone mesenchymal stem cells (BMSCs) to repair bone microdamage diminishes with age, and the accumulation of bone microdamage increases the risk of osteoporotic fracture. There is a lack of effective means to promote the repair of bone microdamage in aged patients with osteoporosis. Exosomes have been shown to be related to the osteogenic differentiation of BMSCs. Here, we aimed to evaluate the changes in the osteogenic differentiation capacity of BMSCs in aged osteoporotic rats after fatigue loading and the treatment potential of serum exosomes from young rats. Methods The tibias of six aged osteoporotic rats were subjected to fatigue loading in vivo for 2 weeks, and the bone microdamage, microstructures, and mechanical properties were assessed. Subsequently, BMSCs were extracted to evaluate their proliferation and osteogenic differentiation abilities. In addition, the BMSCs of aged osteoporotic rats after fatigue loading were treated with serum exosomes from young rats under osteogenic induction conditions, and the expression of osteogenic-related miRNAs was quantified. The osteogenetic effects of miRNA-19b-3p in exosomes and the possible target protein PTEN was detected. Results Obvious bone microdamage at the fatigue load stress point, the bone microstructure and biomechanical properties were not obviously changed. A decreased osteogenic differentiation ability of BMSCs was observed after fatigue loading, while serum exosomes from young rats highly expressing miRNA-19b-3p improved the decreased osteogenic differentiation ability of BMSCs. Transfection with miRNA-19b-3p mimic could promote osteoblastic differentiation of BMSCs and decreased the expression of PTEN. After transfection of miRNA-19b-3p inhibitor, the promotional effect of exosomes on bone differentiation was weakened. Treatment with transfected exosomes increased the expression of PTEN. Conclusion Serum exosomes derived from young rats can improve the decreased osteogenic differentiation ability of BMSCs in aged rats with osteoporosis after fatigue loading and can provide a new treatment strategy for the repair of bone microdamage and prevention of fractures.

Kidney disease is manifested in a wide variety of phenotypes, many of which have an important hereditary component. To delineate the genotypic and phenotypic spectrum of pediatric nephropathy, a multicenter registration system is being implemented based on the Chinese Children Genetic Kidney Disease Database (CCGKDD). In this study, all the patients with kidney and urological diseases were recruited from 2014 to 2020. Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features. The genetic diagnosis was confirmed in 883 of 2256 (39.1%) patients from 23 provinces in China. Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome (SRNS, 23.5%), glomerulonephritis (GN, 32.2%), congenital anomalies of the kidney and urinary tract (CAKUT, 21.2%), cystic renal disease (3.9%), renal calcinosis/stone (3.6%), tubulopathy (9.7%), and chronic kidney disease of unknown etiology (CKDu, 5.8%). The pathogenic variants of 105 monogenetic disorders were identified. Ten distinct genomic disorders were identified as pathogenic copy number variants (CNVs) in 11 patients. The diagnostic yield differed by subgroups, and was highest in those with cystic renal disease (66.3%), followed by tubulopathy (58.4%), GN (57.7%), CKDu (43.5%), SRNS (29.2%), renal calcinosis /stone (29.3%) and CAKUT (8.6%). Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions. We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed. Our data demonstrate the utility of family-based exome sequencing, and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

BackgroundTo demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME).MethodsA 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline.ResultsA total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.ConclusionThe use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept.Trial registration numberNCT02194634.

The stigma of saffron, a precious spice widely used in the world, takes only 7.4% (w/w) of the total weight of the flower, resulting in wasting the rest 92.6% of the flower. The utilization of the waste saffron floral bio-residues (SFB) has hence attracted people’s attention. In this paper, ultrasound-assisted extraction (UAE) associated with macroporous resin (MPR) purification step was successfully applied to enrich antioxidant flavonoid in SFB extract for the first time, resulting in significant increase in flavonoid content compared with other extraction method reported in literatures. The yield of the extract was up to 10%, and the content of kaempferol-3-O-sophoroside (KS) in the obtained extract was more than 50%, which was much higher than the total flavonoid content (2.05–19.2%) reported in other literatures. UAE procedure was optimized by studying the influence of parameters, e.g., extracting solvent, time, temperature and sample–solvent ratio, based on contents of KS and delphinidin-3,5-di-O-glucoside (DG) and the antioxidant activity of the extract. Further enrichment of flavonoid was achieved by D-101 MPR with optimum purification conditions. Furthermore, 52 flavonoids, 8 alkaloids and 10 polyols were identified or putatively characterized from the SFB extract using UPLC-MS, and the contents of KS and DG were determined to be 501.90 and 22.01 mg/g, respectively. Besides, the SFB flavonoid extract showed good antioxidant activities with IC50 33.79 μg/mL for DPPH scavenging effect and 39.65 μmol/mg trolox for ORAC values

Tumor-associated macrophages (TAMs) generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis, suggesting their potential value as a target in cancer immunotherapy. Chlorogenic acid (CHA) has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype. However, rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials. In this study, mannosylated liposomes are developed for targeted delivery of CHA to TAMs. The immunoregulatory effects of CHA, along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes, are investigated through in vitro and in vivo experiments. The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size, favorable stability, and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects. Further, CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype. Overall, these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype., Graphical abstract Image 1, Highlights • DSPE-PEG-Mannose was prepared to functionalize the liposomes for targeted delivery of CHA to TAMs. • Mannosylated liposomes exhibited preferential accumulation in tumors, thereby promoting the polarization of TAMs. • Mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of chlorogenic acid.

Aim: We investigated the expression of type-I gonadotropin-releasing hormone receptor (GnRHR-I) in human tongue cancer SCC-25 cells and the effects of gonadotropin-releasing hormone (GnRH)-I and its analog triptorelin on SCC-25 cells and the related mechanisms of action. Methods: We used RT-PCR, realtime PCR (qPCR) and western blotting to detect the expression of GnRHR-I mRNA and protein in SCC-25 cells, We also used a Cell Counting Kit-8 (CCK-8) assay to calculate cell viability, after treatment with GnRH-I or triptorelin. Results: Results of agarose gel electrophoresis and DNA sequencing showed that the GnRHR-I mRNA of SCC-25 cells were amplified correctly. Western blotting showed that the protein samples of SCC-25 cells had a specific reaction at approximately 60 kDa. GnRH or triptorelin inhibited the proliferation of SCC-25 cells in a dose-dependent manner. GnRH-I and triptorelin at the same concentrations did not significantly differ in inhibiting the proliferation of SCC-25 cells (10 µg/ml: P=0.44,20 µg/ml: P=0.57, 40µg/ml: P=0.28,80 µg/ml: P=0.051). Results of qPCR showed that triptorelin treatment led to stronger inhibition of GnRHR-I mRNA expression in SCC-25 cells than did GnRH-I treatment. (P

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability., Graphical abstract In this study, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles.Image 1

Wujun Dong1,2 ,* Jun Ye1,2 ,* Weijue Wang,1,2 Yanfang Yang,1,2 Hongliang Wang,1,2 Tong Sun,1,2 Lili Gao,1,2 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuling LiuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of ChinaTel +86 10 89285188Fax +86 10 89285190Email ylliu@imm.ac.cnPurpose: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein.Methods: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein.Results: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation.Conclusion: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.Keywords: lecithin/chitosan nanoparticles, transdermal delivery, phospholipid complex, baicalein

Telomeres are structures enriched in repetitive sequences at the end of chromosomes. In this study, using the telomere primer AA(CCCTAAA)3CCC for the single primer PCR, two DNA sequences were obtained from Gossypium hirsutum (Linnaeus, 1753) accession (acc.) TM-1. Sequence analysis showed that the two obtained sequences were all rich in A/T base, which was consistent with the characteristic of the telomere-associated sequence (TAS). They were designated as GhTAS1 and GhTAS2 respectively. GhTAS1 is 489 bp long, with 57.6% of A/T, and GhTAS2 is 539 bp long, with 63.9% of A/T. Fluorescence in situ hybridization results showed that both of the cloned TASs were located at the ends of the partial chromosomes of G. hirsutum, with the strong signals, which further confirmed that GhTAS1 and GhTAS2 were telomere-associated sequences including highly tandemly repetitive sequences. Results of blast against the assembled genome of G. hirsutum showed that GhTAS sequences may be missed on some assembled chromosomes. The results provide important evidence for the evaluation of the integrity of assembled chromosome end sequences, and will also contribute to the further perfection of the draft genomes of cotton.

Deformable nanovesicles (DNVs) have been used in the buccal delivery of biomacromolecules due to their ability to enhance drug penetration. However, no breakthroughs have been made until now due to limited understanding of the factors affecting in vivo buccal delivery. In this study, we designed a series of DNVs, based on an insulin–phospholipid complex (IPC-DNVs), to investigate the influence of drug dose, buccal administration methods, and key quality characteristics of IPC-DNVs for buccal delivery. IPC-DNVs showed a non-linear dose–response relationship between 8 and 12 IU. There was no significant effect of drug delivery site (sublingual mucosa/buccal mucosa) or ligation time (15 or 30 min) on buccal absorption of IPC-DNVs. However, the area above the curve of reduction in blood glucose level overtime (AAC0–6h) for oral mucosa administration was significantly higher than that for buccal mucosa administration. Increasing the drug concentration in IPC-DNVs led to a decrease in AAC0–6h. This might be due to local leakage of DNVs, while squeezing through biological barriers with high concentration of insulin, thus hindering the subsequent delivery of DNVs. IPC-DNVs, measuring 80–220 nm in size, did not significantly affect AAC0–6h. However, when the size was increased to approximately 400 nm, AAC0–6h decreased, thus suggesting that IPC-DNVs with reasonable size were more effective. Additionally, increased deformability of IPC-DNVs might cause drugs to leak easily, thus reducing the promoting effect of buccal absorption. Our results clarified the effect of characteristics of IPC-DNVs on buccal delivery in vivo and provided meaningful support for the design of dosage form of DNVs.

Background: Respiratory syncytial virus (RSV) can cause varying degrees of lung inflammation in children. Qingfei Oral Liquid (QF) is effective in treating childhood RSV-induced lung inflammation (RSV-LI) in clinics, but its pharmacological profiles and mechanisms remain unclear.Methods: This study combined network Pharmacology, lipidomics, pharmacodynamics, and pathway validation to evaluate the therapeutic mechanisms of QF. Using Cytoscape (v3.8.2) and enrichment analyses from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), a global view of the putative compound-target-pathway network was created. The corresponding lipidomic profiles were then used to detect differently activated lipids, revealing the metabolic pathway, using ultra-high-performance liquid chromatography linked to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Meanwhile, the in vivo efficiency of QF, the enrichment pathway, and the excessive autophagy inhibition mechanisms were validated in RSV-infected mice models.Results: The network pharmacology results demonstrated 117 active compounds acted directly upon 101 core targets of QF against RSV-LI. The most significantly enriched pathway was the PI3K/Akt/mTOR signaling pathway (p < 0.05). In addition, untargeted lipidomics were performed, and it was revealed that higher lung levels of DAG 30:0, DAG 30:5, DAG 32:0, DAG 16:0_18:0, DAG 17:0_17:0, DAG 34:1, DAG 36:0, DAG 36:1 in the RSV-LI group were decreased after QF administration (FDR < 0.05, FC > 1.2). Lipin-1, a key enzyme in DAG synthesis, was increased in the RSV-LI mouse model. Animal experiments further validated that QF inhibited the PI3K/Akt/mTOR signaling pathway, with lower lung levels of phosphorylated PI3K, AKT and mTOR, as well as its related proteins of lipin-1 and VPS34 (p < 0.01). Finally, pharmacodynamic investigations indicated that QF reduced airway inflammation caused by excessive autophagy by decreasing lung levels of RSV F and G proteins, Beclin-1, Atg5, and LC3B II, IL-1 and TNF-α (p < 0.05).Conclusion: Lipidomic-based network pharmacology, along with experimental validation, may be effective approaches for illustrating the therapeutic mechanism of QF in the treatment of RSV-LI.

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

Background Golden2-Like (GLK) transcription factors are a type of transcriptional regulator in plants. They play a pivotal role in the plant physiological activity process and abiotic stress response. Methods In this study, the potential function of GLK family genes in Gossypium hirsutum was studied based on genomic identification, phylogenetic analysis, chromosome mapping and cis-regulatory elements prediction. Gene expression of nine key genes were analyzed by qRT-PCR experiments. Results Herein, we identified a total of 146 GhGLK genes in Gossypium hirsutum, which were unevenly distributed on each of the chromosomes. There were significant differences in the number and location of genes between the At sub-genome and the Dt sub-genome. According to the phylogenetic analysis, they were divided into ten subgroups, each of which had very similar number and structure of exons and introns. Some cis-regulatory elements were identified through promoter analysis, including five types of elements related to abiotic stress response, five types of elements related to phytohormone and five types of elements involved in growth and development. Based on public transcriptome data analysis, we identified nine key GhGLKs involved in salt, cold, and drought stress. The qRT-PCR results showed that these genes had different expression patterns under these stress conditions, suggesting that GhGLK genes played an important role in abiotic stress response. This study laid a theoretical foundation for the screening and functional verification of genes related to stress resistance of GLK gene family in cotton.

Background and aims Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control. Methods Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of the 29 cancer groups were calculated based on sex, age, region, and country. In addition, separate analyses were performed for major cancer types. Results In 2019, more than 10 million people died from cancer, which was approximately twice the number in 1990. Tracheal, bronchus, and lung (TBL) cancers collectively showed the highest death rate, and the ASDR of pancreatic cancer increased by 24%, which was cancer with the highest case fatality rate (CFR). The global cancer ASIR showed an increasing trend, with testicular cancer, thyroid cancer, and malignant skin melanoma showing a significant increase. The ASDR and ASIR of cancer in males were about 1.5 times higher than that in females. Individuals over 50 years had the highest risk of developing cancer, with incidences and deaths in this age group accounting for more than 85% of cancers in all age groups. Asia has the heaviest cancer burden due to its high population density, with esophageal cancer in this region accounting for 53% of the total fatalities related to this type of cancer in the world. In addition, the mortality and morbidity of most cancers increased with the increase in the development or socio-demographic index (SDI) in the SDI regions based on the World Bank's Human Development Index (HDI), with cancer characteristics varying in the different countries globally. Conclusions The global cancer burden continues to increase, with substantial mortality and morbidity differences among the different regions, ages, countries, gender, and cancer types. Effective and locally tailored cancer prevention and control measures are essential in reducing the global cancer burden in the future.

BackgroundMesenteric lymph nodes (MLNs) are critical draining lymph nodes of the immune system that accommodate more than half of the body’s lymphocytes, suggesting their potential value as a cancer immunotherapy target. Therefore, efficient delivery of immunomodulators to the MLNs holds great potential for activating immune responses and enhancing the efficacy of antitumor immunotherapy. Self-microemulsifying drug delivery systems (SMEDDS) have attracted increasing attention to improving oral bioavailability by taking advantage of the intestinal lymphatic transport pathway. Relatively little focus has been given to the lymphatic transport advantage of SMEDDS for efficient immunomodulators delivery to the MLNs. In the present study, we aimed to change the intestinal lymphatic transport paradigm from increasing bioavailability to delivering high concentrations of immunomodulators to the MLNs.MethodsChlorogenic acid (CHA)-encapsulated SMEDDS (CHA-SME) were developed for targeted delivery of CHA to the MLNs. The intestinal lymphatic transport, immunoregulatory effects on immune cells, and overall antitumor immune efficacy of CHA-SME were investigated through in vitro and in vivo experiments.ResultsCHA-SME enhanced drug permeation through intestinal epithelial cells and promoted drug accumulation within the MLNs via the lymphatic transport pathway. Furthermore, CHA-SME inhibited tumor growth in subcutaneous and orthotopic glioma models by promoting dendritic cell maturation, priming the naive T cells into effector T cells, and inhibiting the immunosuppressive component. Notably, CHA-SME induced a long-term immune memory effect for immunotherapy.ConclusionsThese findings indicate that CHA-SME have great potential to enhance the immunotherapeutic efficacy of CHA by activating antitumor immune responses.

The present study aimed to investigate the effects of zhike pingchuan granules (ZKPC) on bronchial asthma and the underlying mechanism. A bronchial asthma mouse model was established by aerosol inhalation of ovalbumin. The changes in lung pathomorphology were observed by hematoxylin and eosin staining. The levels of IL-1β, TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) and serum were detected by corresponding ELISA kits. Levels of reactive oxygen species, malondialdehyde and superoxide dismutase in lung tissues were analyzed using corresponding kits. The expression of proteins related to apoptosis and the IL-6/janus kinase 2 (JAK2)/STAT3 pathway was detected by western blot analysis. The results showed that ZKPC significantly restored the dry/wet ratio and alleviated lung pathomorphology of bronchial asthmatic mice. In addition, ZKPC inhibits inflammation, oxidative stress levels and cell apoptosis in bronchial asthmatic mice and also suppressed the IL-6/JAK2/STAT3 pathway. Fedratinib (a JAK2 inhibitor) further strengthened the alleviative effects of ZKPC on bronchial asthma. In conclusion, ZKPC improved bronchial asthma by suppressing the IL-6/JAK2/STAT3 pathway.

Caregivers of people with dementia (PwD) frequently experience poor physical, mental and social health. Over the past decade, several guidelines have offered recommendations on supporting caregivers to improve their health outcomes. This systematic review aimed to assess the quality and evidence base of guidelines on supporting caregivers of PwD and review the content of their recommendations on caregiver support to facilitate the adoption and implementation of a specific guideline among policymakers and practitioners. A systematic search for guidelines on supporting caregivers of PwD was performed using journal databases, websites of guideline development organisations and professional dementia-related societies from inception to 30 June 2020. Four independent reviewers performed the quality assessment of the included guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. A thematic synthesis was used to analyse the content of recommendations on caregiver support extracted from the included guidelines by two independent reviewers. The strength of recommendations and level of evidence were reclassified and analysed. Literature searches identified nine guidelines. Their quality was variable. The applicability domain on AGREE II yielded the lowest median score (62.2%; range: 18.6%-86.6%), suggesting that some guidelines lacked applicability in certain fields, leaving them open to interpretation. Most evidence underlying the extracted recommendations was rated as Levels 3 (51.3%) and 4 (31.1%). High-quality evidence is required to fortify these recommendations. The nine guidelines covered six themes-assessment, education, skill training, information provision, psychosocial support and general support policies-which can guide future policies and interventions of caregiver support. The recommendations extracted were consistent across guidelines, but each guideline failed to cover all six themes. Thus, more applicable and comprehensive guidelines that fully address all themes of support for caregivers of PwD are needed.

Hepatocellular carcinoma (HCC) is a common and high-mortality cancer worldwide. Numerous microRNAs have crucial roles in the progression of different cancers. However, identifying the important microRNAs and the target biological function of the microRNA in HCC progression is difficult. In this study, we selected highly expressed microRNAs with different read counts as candidate microRNAs and then tested whether the microRNAs were differentially expressed in HCC tumour tissues, and we found that their expression was related to the HCC prognosis. Then, we investigated the effects of microRNAs on the cell growth and mobility of HCC using a real-time cell analyser (RTCA), colony formation assay and subcutaneous xenograft models. We further used deep-sequencing technology and bioinformatic analyses to evaluate the main functions of the microRNAs. We found that miR-103a was one of the most highly expressed microRNAs in HCC tissues and that it was upregulated in HCC tissue compared with the controls. In addition, high miR-103a expression was associated with poor patient prognosis, and its overexpression promoted HCC cell growth and mobility. A functional enrichment analysis showed that miR-103a mainly promoted glucose metabolism and inhibited cell death. We validated this analysis, and the data showed that miR-103a promoted glucose metabolism-likely function and directly inhibited cell death via ATP11A and EIF5. Therefore, our study revealed that miR-103a may act as a key mediator in HCC progression.

Background: EGFR-TKIs are prone to develop acquired drug resistance in colorectal cancer and are only applicable in Kras wild type colorectal cancer patients. This study aimed to determine the reasons for the poor treatment efficacy of TKIs in Kras mutant CRC and to improve the treatment effect. Method: The RTK Phosphorylation Membrane array was used to detect and screen changes in phosphorylated protein levels in KRAS mutant-resistant CRC cells. qRT-PCR, western blot and TCGA database were applied for reporting the expression of ERGR and ErbB3 in CRC. Luciferase reporter and western blot examined the network of miR-323a-3p. RTCA, colony formation, CCK-8, caspase-3/7 activity and Flow cytometry probed the impacts of miR-323a-3p on CRC cell growth.Results: We illustrated that ErbB3 and EGFR were activated in gefitinib-resistant Kras mutant colorectal cancer cell lines. ErbB3 is highly expressed in Kras mutant patient tissues, and patients with ErbB3high/EGFRhigh had a poorer prognosis. Mechanically, We found and verified that the tumor suppressor miR-323a-3p simultaneously directly targeted EGFR/ErbB3 and inhibited tumor cell growth by activating the apoptosis pathway. Further functionality studies identified miR-323a-3p synergized with gefitinib to inhibit tumor growth, and this synergy prevented the development of acquired resistance to gefitinib in CRC cell lines.Conclusion: Accordingly, these data indicate that Kras mutant CRC TKI resistance occurs due to the activation of EGFR and ErbB3. Thus, miR-323a-3p has the potential to treat Kras-mutated colorectal cancer by targeting ErbB3/EGFR.

Allergic rhinitis (AR) is one of the most common allergic diseases in children and it can lead to physical and mental health problems. Traditional Chinese medicine (TCM) plays an important role in understanding the phenotypes and treatment of AR. However, there are currently no normative clinical practice guidelines (CPGs) for the treatment of AR in children. The study aimed to develop an evidence-based CPG for the treatment of AR in children with TCM. Systematic literature research, expert questionnaire, and clinical evaluation after three rounds of surveys were adopted to form recommendations for treating children with AR using the Delphi method. Depending on the clinical manifestations, we finally recommended two decoctions with two Chinese patent medicines for an acute attack of AR and two decoctions for a chronic period of AR. For the acute attack of AR in children, Xinyi Qingfei decoction, Wenfei Zhiliu decoction, Xinqin granules, and Xinyi Biyan pills were suggested, whereas for the chronic period of AR, Buzhong Yiqi and Jingui Shenqi decoctions were recommended. The four external treatment methods suggested for the prevention and care of AR were body acupuncture, moxibustion, auricular point pressing, and acupoint application. The recommended levels of the suggested TCM strategies ranged from Grade B to D, indicating the weakness of the recommendations. TCM has the potential to offer new insights into phenotypes and the management of AR worldwide; however, more high-quality clinical studies are needed to improve the quality of evidence.过敏性鼻炎是儿童最常见的疾病之一,对儿童的身心健康产生一定的负面影响。中医药在儿童过敏性鼻炎的辨证分型及治疗中起着重要作用, 但目前尚缺乏规范的临床实践指南。本研究旨在制定儿童过敏性鼻炎的循证性中医药临床实践指南, 采用了系统的文献研究、专家问卷调查以及三轮调查后的临床评价, 并运用德尔菲法形成了儿童过敏性鼻炎的中医药推荐疗法。根据不同的临床表现, 我们最终推荐了“辛夷清肺饮、温肺止流丹”两种复方结合“辛芩颗粒、辛夷鼻炎丸”两种中成药来治疗急性期儿童过敏性鼻炎；对于慢性期儿童过敏性鼻炎, 我们推荐了补中益气汤和金匮肾气丸；同时本研究提出“体针、艾灸、耳穴、穴位贴敷”等四种外治法可用于儿童过敏性鼻炎的预防与调护。以上治疗方案的推荐等级从B级到D级不等, 总体推荐力度较弱。因此, 本研究认为中医药辨证论治儿童过敏性鼻炎具有较大的潜力, 可为本病诊疗提供新的见解, 但仍然需更多高质量的临床研究来提高证据的质量。.

Background and aims Cancer has become the second most serious disease threatening human health, followed by cardiovascular diseases. This study aimed to quantitatively estimate the mortality, morbidity, and analyze the trends of 29 cancer groups in 195 countries/regions between 1990 and 2017. Methods Detailed information of 29 cancer groups were collected from the Global Burden of Disease (GBD) study in 2017 and age-standardized incidence rates (ASIR) and age-standardized death rates (ASDR) of 29 cancer groups were calculated based on gender, age, region, and country. Trend analyses were conducted for major cancer types. Results In 2017, the global death population caused by cancer reached 9 million, which was nearly twice the number in 1990. The ASDR and ASIR of cancer in males were about 1.5 times those of females. Breast cancer showed the highest mortality rate in females in 2017. Individuals aged over 50 are at high risk of developing cancer and the number of cases and deaths in this age group accounted for more than 80% of all cancers in all age groups. Asia has the heaviest cancer burden due to its large population density. Different cancers in varied countries globally have their own characteristics. The ASDR and ASIR of some major cancers demonstrated changes from 1990 to 2017. Conclusions Analyses of these data provided basis for future investigations to the common etiological factors, leading to the occurrence of different cancers, the development of prevention strategies based on local characteristics, socioeconomic and other conditions, and the formulation of more targeted interventions.

SiGe is one of the most promising strain relaxed buffer at advanced technology nodes. In this paper, the effects of pentapotassium; 2-[bis[2-[bis(carboxylatomethyl)amino]ethyl] amino]acetate (DTPA-5K) and triethanolamine (TEA) on Si0.5Ge0.5 chemical mechanical polishing (CMP) under alkaline condition were investigated. The results show that, DTPA-5K is a corrosion and rate enhancer for Si0.5Ge0.5. GeO2 and the silicon sub-oxide are believed to be generated on Si0.5Ge0.5 surface in DTPA-5K solution. The Si0.5Ge0.5 removal rate and its selectivity to TEOS are both proportional to DTPA-5K concentration. However, DTPA-5K has an impact on the slurry stability. With proper DTPA-5K concentration to ensure colloidal stability, the surface roughness of Si0.5Ge0.5 can be improved by triethanolamine (TEA). An optimized slurry formulation in the presence of DTPA-5K and TEA yielded a high Si0.5Ge0.5 removal rate, an acceptable within-wafer non-uniformity (WIWNU), very low surface roughness and desirable selectivity to TEOS. A CMP mechanism for this system is also proposed.

Background: Tumor-associated macrophages (TAMs) are critical in tumor progression and metastasis. Selective targeting of TAMs holds great potential to ameliorate the immunosuppressive tumor microenvironment and enhance the efficacy of antitumor therapy. Various liposomes have been developed to target TAMs via cell-specific surface receptors either to deplete or re-educate TAMs. Since immuno-stimulation often initiates with the interaction of nanocarriers with the innate immunity cells such as macrophages, the intrinsic impact of drug-free liposomes on macrophage activation and polarization via cell interaction is one of the most critical issues in nanomedicine for promoting effective immunotherapy. Methods: In this study, conventional bare liposomes, PEGylated liposomes, and mannosylated liposomes were developed and the cytotoxicity, cellular internalization, immunostimulatory activity, targeting efficiency, antitumor efficacy, and mechanism were evaluated in vitro and in vivo. Results: All liposomes displayed an ideal particle size, good biocompatibility, and controlled release behavior. Mannosylated liposomes exhibited superior in vitro cellular internalization and tumor spheroid penetration with the aid of the mannose receptor-mediated TAMs-targeting effects. In particular, mannosylated liposomes promoted the polarization of both M0 and M2 to the M1 phenotype by enhancing the expression ratio of CD86/CD206 in vitro. Of note, mannosylated liposomes could inhibit G422 glioma tumor growth, which may be attributed to the polarization of TAMs, as evidenced by the reduction in expression level of the TAMs surface marker. Conclusion: These results indicate the potential value of mannosylated liposomes in the design of a rational delivery system to enhance the antitumor immune efficacy of immunomodulators by inducing a shift from the M2 to the M1 phenotype.

The frequency of convergence insufficiency was determined in a sample of Chinese high school students. The associations between the frequency of convergence insufficiency, gender, refractive error and accommodative insufficiency were investigated.This was a single-site, prospective cross-sectional study. In total, 928 eligible teenagers (mean age 15.9 ± 0.8) from a local high school in Guangzhou, Guangdong Province, China participated in this study. Refraction and binocular vision tests were performed on all eligible participants. The following three signs were used to classify participants: sign 1, exophoria at near at least 4The number and frequency of individuals with 3-Sign, 2-Sign, and 1-Sign convergence insufficiency as well as no convergence insufficiency group were 25 (2.7 per cent), 119 (12.8 per cent), 303 (32.6 per cent) and 481 (51.8 per cent), respectively. Gender (χCompared to the data from school- and clinic-based populations in the USA and South Africa, the data from this sample of Chinese high school students showed a lower frequency of 3-Sign convergence insufficiency (2.7 per cent). Convergence insufficiency was associated with refractive error, gender and accommodative insufficiency.

Traditional Herbal Medicine (THM) has been used for thousands of years, and is popular worldwide due to its effectiveness in a variety of diseases. THM has also formed the basis of the discovery of modern drugs like artemisinin and paclitaxel. However, at present, studies that focus on development in the field of THM are stagnant because currently, the effective ingredients in the herbal formulations and the ambiguity of the underlying mechanisms of action are unknown. In this review, we have investigated the studies available that focused on the efficacy, active ingredients and bioavailability of THM, and the function of gut microbiota in THM-mediated treatment of disease. We hypothesized that most THMs treat diseases via three mechanisms: (1) metabolizing into active metabolites by the action of gut microbiota, (2) regulation of gut microbiota balance, and (3) regulating the fermentation products of the gut microbes. Therefore, focusing on these aspects can help elucidate the pharmacodynamic constituents of THM preparations, and their therapeutic mechanisms of action.

Background Post-operative pneumonia (Pop) following meningioma surgery is the dominant systemic complication which could cause serious threats to patients. It is unclear whether hematological biochemical markers are independently associated with the Pop. This study attempted to perform a more comprehensive study of taking both clinical factors and hematological biomarkers into account to promote the management of patients after meningioma surgery. Methods We collected clinical and hematological parameters of 1156 patients undergoing meningioma resection from January 2009 to January 2013. According to whether the symptoms of pneumonia had manifested,patients were divided into the Pop group and the Non-Pop group. We analyzed the distinctions of clinical factors between the two groups. We successively performed univariate and multivariate regression analysis to identify risk factors independently associated with the Pop. Results 4.4% patients infected with the Pop (51 of 1156). The median age at diagnosis of the Pop patients was significantly older than the Non-Pop group (p = 0.002). There were strike distinctions of post-operative hospital stays between two groups, with 21 days and 7 days each (p

Prenatal diagnostics holds great significance for pregnant women desiring healthy babies. Fetal nucleated red blood cells (fNRBCs), bearing the complete genome of the fetus, have been regarded as an important biomarker for noninvasive prenatal diagnostics (NIPD). The high-performance detection and enrichment of fNRBCs from maternal blood, especially during early pregnancy, is urgently needed for NIPD, which, unfortunately, remains a big challenge for early-pregnancy fNRBC isolation. In this study, we developed an innovative platform based on silica microbeads for fNRBC isolation and release in early pregnancy. Microbeads were coated with self-assembled MnO2 nanoparticles (SiO2@MnO2) and then modified with a specific antibody. Benefiting from the three-dimensional nanostructure of the MnO2 nanoparticles, the isolation efficiency of the fNRBCs was enhanced. Subsequently, fNRBCs were released via dissolving the MnO2–nanoparticle coating using oxalic acid. We successfully isolated fNRBCs from the maternal peripheral blood samples of 20 pregnant women in the early pregnancy period, ranging from 41 to 62 gestational days. More importantly, the fetal origin of isolated cells was confirmed via fluorescent in situ hybridization and short tandem repeat analysis. This platform based on SiO2@MnO2 microbeads has verified the existence of fNRBCs in early-pregnancy maternal blood and is a promising approach for NIPD in early pregnancy.

The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) nearly 2.7-fold during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia, reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.

Ethnopharmacological relevance Fufang Danshen Tablet (FDT) is a traditional Chinese medicine (TCM) formula composed of three Chinese medicinal materials comprising Salviae Miltiorrhizar Radix et Rhizoma (Dan-Shen in Chinese), Notoginseng Radix et Rhizoma (San-Qi), and Borneolum Syntheticum (Bing-Pian). It has been documented to exert significant effects in promoting blood circulation and removing blood stasis, and become a frequently used formula in the treatment of cardiovascular and cerebrovascular diseases. Aim of the review To systematically analyze and summarize the research findings concerning the chemical composition, quality control, pharmacokinetics, pharmacological properties, clinical applications, and toxicity of FDT, so as to point out some typical problems and provides opinions for future study. Materials and methods Literatures involving FDT were collected from online scientific databases including China National Knowledge Infrastructure, WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and Google Scholar up to March 2021. All eligible studies are analyzed and summarized in this review. Results This review summarizes reported results concerning the post-marketing quality and efficacy of FDT. Some problems are pointed out for FDT. Hereon we propose several directions for future study: (a) improvement of quality control based on exact overall chemical profiles, entire production process monitoring, and biopotency-associated multi-index content determination method; (b) clarification of functional mechanisms focused on pharmacokinetic profiles in human, interplay with gut microbiota, and integration of multi-omics technologies; (c) reconfirmation of clinical effectiveness and safety from large-scale clinical studies based on evidence-based medicine. Conclusions FDT is a typical TCM formula in treating cardiovascular and cerebrovascular diseases, but there are also some troubles. Future studies should focus on the improvement of quality control, the clarification of functional mechanisms, as well as the reconfirmation of clinical effectiveness and safety.

OBJECTIVE This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS After treatment for 24 weeks, the change in HbA1c was –0.93% (95% CI –1.03 to –0.83) (–10.2 mmol/mol [–11.3 to –9.1]) and –0.87% (–0.99 to –0.76) (–9.5 mmol/mol [–10.8 to –8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was –0.05% (95% CI –0.18 to 0.07) (–0.5 mmol/mol [–2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.

Scutellaria baicalensis Georgi., a plant used in traditional Chinese medicine, has multiple biological activities, including anti-inflammatory, antiviral, antitumor, antioxidant, and antibacterial effects, and can be used to treat respiratory tract infections, pneumonia, colitis, hepatitis, and allergic diseases. The main active substances of S. baicalensis, baicalein, baicalin, wogonin, wogonoside, and oroxylin A, can act directly on immune cells such as lymphocytes, macrophages, mast cells, dendritic cells, monocytes, and neutrophils, and inhibit the production of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α, and other inflammatory mediators such as nitric oxide, prostaglandins, leukotrienes, and reactive oxygen species. The molecular mechanisms underlying the immunomodulatory and anti-inflammatory effects of the active compounds of S. baicalensis include downregulation of toll-like receptors, activation of the Nrf2 and PPAR signaling pathways, and inhibition of the nuclear thioredoxin system and inflammation-associated pathways such as those of MAPK, Akt, NFκB, and JAK-STAT. Given that in addition to the downregulation of cytokine production, the active constituents of S. baicalensis also have antiviral and antibacterial effects, they may be more promising candidate therapeutics for the prevention of infection-related cytokine storms than are drugs having only antimicrobial or anti-inflammatory activities.

Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers, and so on. In this review, we aim to offer a summary of chemical structure and properties, anti-cancer activities, drug delivery systems and combination therapy of GA, which might provide a reference to promote the development and clinical application of GA.

Background: Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. Aims: The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. Methods: The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. Results: The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. Conclusions: The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.

Chromosome painting is one of the key technologies in cytogenetic research, which can accurately identify chromosomes or chromosome regions. Oligonucleotide (oligo) probes designed based on genome sequences have both flexibility and specificity, which would be ideal probes for fluorescence in situ hybridization (FISH) analysis of genome structure. In this study, the bulked oligos of the two arms of chromosome seven of cotton were developed based on the genome sequence of Gossypium raimondii (DD, 2n = 2× = 26), and each arm contains 12,544 oligos. Chromosome seven was easily identified in both D genome and AD genome cotton species using the bulked chromosome-specific painting probes. Together with 45S ribosomal DNA (rDNA) probe, the chromosome-specific painting probe was also successfully used to correct the chromosomal localization of 45S rDNA in G. raimondii. The study reveals that bulked oligos specific to a chromosome is a useful tool for chromosome painting in cotton.

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

Background This study aimed to evaluate the visual and morphological outcomes of intravitreal anti-VEGF therapy and the recurrence for idiopathic choroidal neovascularization (ICNV). Methods This retrospective study included 35 patients (35 eyes) with ICNV from July 2012 to October 2017. All patients received 1 intravitreal anti-VEGF injection followed by pro re nata injections until there was no sign of ICNV activity. This was defined as the first follow-up period. To evaluate ICNV recurrence, we continued to follow-up 27 of the 35 patients for at least 2 years after the initial diagnosis, and the longest follow-up period was 5 years. Additional injection was performed when ICNV recurred. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded and morphological improvement in optical coherence tomography (OCT) was assessed. Parameters that affect prognosis and recurrence were analysed. Results The mean follow-up period was 168.0 ± 34.82 weeks. Mean BCVA improved from 56.20 ± 14.13 letters at baseline to 73.31 ± 12.57 letters (PP P = 0.026) in OCT: the lesion had completely subsided with recovery of the foveal contour. Those with high baseline BCVA (more than 60 letters) showed significant resolution of CNV lesions (P = 0.036). ICNV recurred in six patients (22.2%), 1 of whom experienced 2 recurrences. The mean timing of recurrence was 90.83 ± 49.02 weeks after diagnosis. There was no significant correlation between ICNV recurrence and the morphological improvement (P = 0.633). The final BCVA in patients with recurrence did not differ from that in patients without recurrence (P = 0.065). Conclusions Intravitreal anti-VEGF therapy on a pro re nata basis was effective for treating ICNV. High baseline BCVA indicated a better prognosis. Re-treatment with anti-VEGF could effectively lead to resolution of recurrent ICNV. Disease recurrence had no significant effect on final visual prognosis and had no correlation with the morphological improvement during treatment, suggesting that follow-up for subsequent monitoring should be performed in all ICNV patients.

We present 2 cases of coronavirus disease 2019 (COVID-19)–associated severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the third trimester of pregnancy. Both mothers and newborns had excellent outcomes. We failed to identify SARS-CoV-2 in all of the products of conception and the newborns. This report provided evidence of low risk of intrauterine infection by vertical transmission of SARS-CoV-2.