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Chiral metallohelix ΛA inhibited amyloid-β aggregation with enantioselectivity in vivo. Beyond the intrinsic bioactivity, alkyne-bearing ΛA was employed as a building block for convenient visualization and versatile modification via click reaction.

We illuminate that cytochrome c (Cyt c) directly interacts with amyloid-β (Aβ) and alters Aβ amyloidogenesis in a peroxide-dependent manner, which demonstrates its new role towards the amyloid pathology associated with Alzheimer's disease.

Irritable bowel syndrome (IBS) is a very common refractory disease. Its exact pathophysiological mechanism is still unclear. Despite the availability of plentiful drugs to control IBS, most patients do not respond well. Ginsenoside Rd is one of the major active components of Panax ginseng, which has been verified to produce various pharmacological actions. However, the role of ginsenoside Rd in modulating smooth muscle contractility is still undefined. The aim of this study is to investigate the effects of ginsenoside Rd on intestinal contractility and related mechanisms in IBS.

As disc fragment completely loses contact with the parent disc and can migrate in all directions of the epidural space, making it appear similar to schwannoma, it is fairly difficult to make a definitive diagnosis for mimicking tumor discs. The aim of this research is to differentially diagnose mimicking tumor discs and schwannomas using coronal magnetic resonance imaging (MRI) of three-dimensional fast-field echo with water-selective excitation (CMRI).Among 76 patients (38 men and 38 women; mean age, 52.88 ± 15.80 [range, 18-78 years]) who were retrospectively examined in this study, 38 were primarily diagnosed with schwannomas and pathologically diagnosed with mimicking tumor discs after surgery, and 38 were primarily diagnosed with neurogenic tumors and pathologically diagnosed with schwannomas after surgery. Open surgery was performed in all the patients between March 2016 and April 2020. The preliminary diagnosis of all patients was considered an intraspinal tumor based on conventional two-dimensional MRI sequences. After open surgery, the final diagnosis was confirmed to mimic a tumor disc or schwannoma based on postoperative pathology reports. The sensitivity, specificity, and reliability of CMRI and conventional MRI for identifying mimicking tumor discs and schwannomas were compared. Chi-square and McNemar tests were used for statistical analyses.Symptoms were considerably relieved in all the patients after surgery. Seven patients had grade 1 extensor digitorum longus, triceps surae, or quadriceps femoris muscle strength prior to surgery. No nerve root injury was observed in any of the patients. CMRI showed significantly higher sensitivity (94.74%) and specificity (94.74%) than conventional MRI (71.05% and 92.11%, respectively; p = 0.012 0.05, and p = 1 0.05, respectively) for differential identification between mimicking tumor discs and schwannomas. Moreover, CMRI showed a higher reliability (kappa value = 0.787) than conventional MRI (kappa value = 0.374).CMRI is a better non-invasive technology for the identification of intraspinal lesions, especially for differentiating between mimicking tumor discs and schwannomas.

The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care).In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing.Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p0·0001). No treatment-related serious adverse events were reported in either group.Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control.Ministry of Science and Technology of China.

In this work, we investigate the relation between the photon sphere radius and the first-order phase transition for the charged Einstein-power-Yang-Mills AdS black hole. Through the analysis, we find with a certain condition there exist the non-monotonic behaviors between the photon sphere radius, the impact parameter, the non-linear Yang-Mills charge parameter, temperature, and pressure. And both the changes of photon sphere radius and impact parameter before and after phase transition can be regarded as the order parameter, their critical exponents near the critical point are equal to the same value 1/2, just like the ordinary thermal systems. These indicate that there maybe exists a universal relation of gravity nearby the critical point for a black hole thermodynamical system. Furthermore, the effect of impact parameter on the deflect angle is also investigated.

Neurosyphilis is a major clinical manifestation of syphilis. In recent years, an increase in neurosyphilis cases has been reported in many countries. The overall incidence of neurosyphilis remains unknown, and there is a lack of understanding of the disease pathogenesis, which hampers clinical management, development of prevention strategies, and control. This article proposes the CARE-NS research strategy to enhance the clinical management of neurosyphilis, which consists of six key features: comprehensive management including multidisciplinary treatment (C), alleviating neurological impairment and sequelae (A), risk factors and clinical epidemiology (R), etiology and pathogenesis (E), new diagnostic indicators and strategies (N), and social impact and cost-effectiveness analysis (S).

Hepatic arterial infusion chemotherapy (HAIC) and Transarterial chemoembolization (TACE) both showed good local efficacy in advanced or unresectable hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis to compare the effect of HAIC with TACE in patients with unresectable HCC.Clinical trials, which were about HAIC or TACE in Patients with unresectable HCC, were identified by searching PubMed, Medline, and EMBASE from January 2010 to March 2022. A meta-analysis was performed to analyze HAIC in comparison with TACE. Treatment response, 1-year overall survival (OS), 2-year OS and serious adverse events were evaluated in this meta-analysis.This meta-analysis included 6 studies. Objective response rate or Partial response in the HAIC group was significantly more than that in the TACE group (P .05). But, stable disease showed no difference between the 2 groups (P = .52). Disease control rate in the HAIC group was better than that in the TACE group (P .05). Progressive disease in the HAIC group was less than that in the TACE group (P .05). In 1-year OS, there was no significant deterioration between the 2 groups (P = .53). There was not significant difference in 2-year OS between the 2 groups (P = .05). serious adverse events in the HAIC group was significantly less than that in the TACE group (P .05).To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.

Robust cytosolic protein delivery requires both efficient protein binding with delivery vehicles and effective protein release after cell internalization. Although a variety of stimuli-responsive c...

ConspectusAlzheimer's disease (AD) is the most common form of dementia and is characterized by memory loss and cognitive decline. Approximately 50 million people worldwide are suffering from AD and related dementias. Very recently, the first new drug targeting amyloid-β (Aβ) aggregates has been approved by the United States Food and Drug Administration, but its efficacy against AD is still debatable. Other available treatments temporarily relieve the symptoms of AD. The difficulty in discovering effective therapeutics for AD originates from its complicated nature, which results from the interrelated pathogenic pathways led by multiple factors. Therefore, to develop potent disease-modifying drugs, multiple pathological features found in AD should be fully elucidated.Our laboratory has been designing small molecules as chemical tools to investigate the individual and interrelated pathologies triggered by four pathogenic elements found in the AD-affected brain: metal-free Aβ, metal-bound Aβ, reactive oxygen species (ROS), and acetylcholinesterase (AChE). Aβ peptides are partially folded and aggregate into oligomers, protofibrils, and fibrils. Aβ aggregates are considered to be neurotoxic, causing membrane disruption, aberrant cellular signaling, and organelle dysfunction. In addition, highly concentrated metal ions accumulate in senile plaques mainly composed of Aβ aggregates, which indicates that metal ions can directly interact with Aβ. Metal binding to Aβ affects the aggregation and conformation of the peptide. Moreover, the impaired homeostasis of redox-active Fe(II/III) and Cu(I/II) induces the overproduction of ROS through Fenton chemistry and Fenton-like reactions, respectively. Dysregulated ROS prompt oxidative-stress-damaging biological components such as lipids, proteins, and nucleic acids and, consequently, lead to neuronal death. Finally, the loss of cholinergic transmission mediated by the neurotransmitter acetylcholine (ACh) contributes to cognitive deficits observed in AD.In this Account, we illustrate the design principles for small-molecule-based chemical tools with reactivities against metal-free Aβ, metal-bound Aβ, ROS, and AChE. More importantly, mechanistic details at the molecular level are highlighted with some examples of chemical tools that were developed by our group. The aggregation of metal-free Aβ can be modulated by modifying amino acid residues responsible for self-assembling Aβ or disassembling preformed fibrils. To alter the aggregation and cytotoxicity profiles of metal-bound Aβ, ternary complexation, metal chelation, and modifications onto metal-binding residues can be effective tactics. The presence and production of ROS are able to be controlled by small molecules with antioxidant and metal-binding properties. Finally, inhibiting substrate access or substrate binding at the active site of AChE can diminish its activity, which restores the levels of ACh. Overall, our rational approaches demonstrate the feasibility of developing small molecules as chemical tools that can target and modulate multiple pathological factors associated with AD and can be useful for gaining a greater understanding of the multifaceted pathology of the disease.

Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.

Background The awareness and willingness to use doxycycline-based syphilis chemoprophylaxis among men who have sex with men (MSM) in China remain largely unknown. Methods We recruited MSM online from Nanjing, Wuhan and Changsha between August and October of 2021, collected data from online survey, analyzed their data using descriptive statistics, and constructed binary logistic regression for factors associated with awareness and willingness to use chemoprophylaxis for syphilis and HIV. Results Of 725 participants (44.0% of which resided in Nanjing, 37.7% in Changsha, and 18.3% in Wuhan), a majority were under 25 years of age; 62.2% had college degrees; 11.3% were HIV positive; and 5.10% had prior syphilis infection. Only 28.83% of participants had heard of syphilis chemoprophylaxis before. Odds of knowing syphilis chemoprophylaxis were higher in those who think it is necessary to have syphilis chemoprophylaxis versus those who think it is unnecessary (P = 0.002), and were higher in those whose acquaintance had chemoprophylaxis experience before (P P = 0.009, P Conclusions We observed elevated interest in syphilis chemoprophylaxis in MSM in our investigational areas, indicating that the combination of HIV and syphilis chemoprophylaxis in China is promising.

Background The uncertainty of how neurosyphilis is diagnosed and treated in clinical settings led us to investigate whether this serious manifestation of syphilis infection is properly managed in China. Methods: This national cross-sectional study of the diagnosis and treatment of neurosyphilis included 1392 clinicians at 398 hospitals located in 116 cities in China. Results: Of 398 hospitals, 244 (61.3%) failed to perform diagnostic laboratory tests and 181 (45.5%) failed to provide recommended treatment for neurosyphilis. Of 1392 clinicians, 536 (38.5%) had previously diagnosed patients with neurosyphilis, but 419 (78.2%) of the latter provided diagnoses that did not meet the criteria set by national guidelines. Of the 485 clinicians who had previously treated patients with neurosyphilis, 280 (57.7%) failed to follow national guidelines for treatment. Analysis indicated that clinicians working in North China (adjusted odds ratio (aOR), 4.24; 95% confidence interval (CI), 1.65–10.88), tertiary hospitals (aOR, 3.23; 95% CI, 1.63–6.41), and hospitals specialising in sexually transmitted infections (aOR, 2.49; 95% CI, 1.24–4.99) were more likely to follow national guidelines for neurosyphilis treatment. Conclusion: Lack of knowledge in disease management poses a great obstacle to prevent the serious consequences of neurosyphilis in Chinese patients. More effective measures are urgently needed to improve this suboptimal situation.

Zingiber cassumunar is an important plant used in traditional medicine and as a natural mosquito repellent. However, the compounds responsible for the repellent activity of the plant are still unknown. The aim of the study is to identify the components of Z. cassumunar essential oil that show repellent activity against Aedes albopictus. We also evaluated the larvicidal and adulticidal activities of Z. cassumunar essential oil against Ae. albopictus. In-cage mosquito repellent experiments showed that Z. cassumunar essential oil possessed moderate repellent activity with a minimum effective dose (MED) of 0.16 ± 0.01 mg/cm2, compared to reference standard N,N-diethyl-3-methylbenzamide (DEET, 0.03 ± 0.01 mg/cm2). Bioassay-guided fractionation identified the major active compound of Z. cassumunar essential oil as (−)-terpinen-4-ol (1) (MED: 0.19 ± 0 mg/cm2). We also found that Z. cassumunar essential oil showed moderate larvicidal activity against first instar larvae of Ae. albopictus with a LC50 (50% lethal concentration) of 44.9 μg/L after 24 h. Fumigation bioassays showed that Z. cassumunar essential oil exhibits moderate adulticidal activity against Ae. albopictus with a LC50 of 5.44%, while (−)-terpinen-4-ol showed significant adulticidal activity with a LC50 of 2.10% after 24 h. This study verifies that the Z. cassumunar essential oil has mosquito repellent activity, and that (−)-terpinen-4-ol is mainly responsible for this activity. Furthermore, this study provides scientific support for the folk usage of Z. cassumunar essential oil as mosquito repellent and indicates that Z. cassumunar essential oil and (−)-terpinen-4-ol can be used as plant-derived repellents and insecticides for mosquito control.

Tumor associated macrophages (TAMs) tend to exhibit tumor-promoting M2 phenotype and contribute to the development of immunosuppressive microenvironment of solid tumors. Reprograming TAMs from M2 into tumoricidal M1 phenotype is robust for stimulating tumor immunosuppressive microenvironment (TIME). In this study, we developed a poly(amidoamine) (PAMAM) derivative dendrimer (denoted as fourth generation-N,N-diethylaminoethyl (G4-DEEA)) for efficient loading of Toll-like receptor 7 and 8 (TLR7/8) agonist (R848) to remodel the TIME for potent cancer immunotherapy. G4-DEEA exhibited a high loading capacity of R848 up to 35.9 wt% by taking advantage of its dendritic structure. The resulting formulation (designated as G4-DEEA@R848) effectively polarized M2 macrophages into M1 phenotype in vitro, and improved the maturation and activation of antigen-presenting cells. In the 4T1 orthotopic breast cancer model, G4-DEEA@R848 showed a stronger tumor inhibitory effect than free drug. The mechanistic studies suggested that G4-DEEA@R848 could significantly stimulate the TIME by repolarizing TAMs into M1 phenotype, reducing the presence of immunosuppressive myeloid cells and increasing the infiltration of tumor cytotoxic T cells. This study provides a simple but effective dendrimer-based strategy to improve the formulation of R848 for improved cancer immunotherapy.

This paper proposes a control method for eliminating direct current (DC) flux from the isolation transformer of a customer service device to avoid magnetic saturation. The method is characterised by injecting zero compensation voltage during a designed time. The period during which no compensation voltage is injected is minimised by adjusting the normal compensation time in the initial stage. For a customer service device, such as a dynamic voltage restorer, the reverse turn-off voltage will introduce extra initial flux. The calculation process based on a trigonometric function also takes into account the effects of the initial flux. The experimental results verify the proposed method to prevent DC flux to the isolation transformer.

Alzheimer's disease (AD), as the primary cause of dementia, has seriously affected millions of people worldwide and brought a very heavy financial and social burden. With the growth of population and aging, the situation will worsen unless efficacious drugs are found to reverse, stop, or even slow down disease progression. More and more evidence has demonstrated that amyloid-β (Aβ) aggregation is an upstream causative factor in AD pathogenesis and then triggers a slew of pathological events. Furthermore, the concentrated redox metal ions in the AD brain, especially Cu(II), can significantly exacerbate Aβ aggregation and contribute to the formation of neurotoxic reactive oxygen species (ROS). Therefore, the inhibition of Aβ aggregation and relief of amyloidosis-initiated neurotoxicity play a critical role in AD treatment. Until now, several methods have been proposed to modulate Aβ aggregation, such as developing aggregation inhibitors to interfere with Aβ assembly via noncovalent interactions, copper chelators to cut off metal-accelerated Aβ aggregation and concomitant cytotoxicity, photooxidation to reduce the hydrophobicity and aggregation tendency of Aβ, thermal dissociation to disrupt amyloid aggregates susceptible to temperature, degradation with artificial protease to fracture the Aβ peptide into small fragments, and the clearance of peripheral Aβ to bypass the obstruction of the BBB and reduce the Aβ burden.In this Account, we focus on our contributions to the development of Aβ-targeted multifunctional molecules and nanoparticles, emphasizing the diversified strategies and synergistic therapeutic effects. These therapeutic agents possess the following multifunctionalities: (1) compared with frequently used aggregation inhibitors restricted by intrinsically feeble and sensitive noncovalent interactions, multifunctional agents can efficiently block Aβ aggregation by exploiting two or more Aβ-specific inhibition strategies simultaneously; (2) apart from regulating Aβ aggregation, multipronged agents can also target and modulate other pathological factors in AD pathogenesis, such as increased oxidative stress, abnormal copper accumulation, and irreversible neuron loss; (3) multifunctional platforms with both diagnostic and therapeutic modalities through integrating in situ imaging, real-time diagnostics, a multitarget direction, stimuli-responsive drug release, and the blood-brain barrier (BBB) translocation features are instrumental in improving drug levels at trouble sites, diminishing off-target adverse reactions, evaluating therapeutic effects, and averting overtreatment.Given the fact that amyloid aggregation, local inflammation, and metal dyshomeostasis are universal biomarkers shared by various neurodegenerative disorders, this Account provides a perspective for the evolution of customized therapeutic agents with multiple reactivities for other neurodegenerative diseases. In addition, recent studies have indicated that Aβ aggregates can enter the nucleus and induce DNA damage and anomalous conformational transition. We also explore the influences of DNA on the biological effects of Aβ aggregates.

During a survey of freshwater fungi in Guizhou Province, China, six hyphomycetous collections were founded on decaying wood from freshwater habitats. These taxa were characterized and identified based on morphology, phylogeny, and culture characteristics. Phylogenetic analysis of combined LSU, SSU, ITS, RPB2 and TEF1α sequence data indicated that our six isolates formed three distinct lineages and were distributed within Fuscosporellaceae and Savoryellaceae. They can be organized as three new species: Fuscosporella guizhouensis, Mucisporaaquatica and Neoascotaiwaniaguizhouensis. Fuscosporella guizhouensis and Neoascotaiwania guizhouensis have sporodochial conidiomata, micronematous conidiophores and dark brown conidia. The former possesses irregularly ellipsoidal conidia with apical appendages, while the latter has fusiform to obovoid conidia. Mucispora aquatica is characterized by macronematous conidiophores, elongating percurrently and dark brown, narrowly obovoid conidia. The detailed, illustrated descriptions and notes for each new taxon are provided, and the species of Fuscosporella is reported for the first time in China.

The ECG profile of Hypertrophic Cardiomyopathy (HCM) includes ST-segment elevation (STE) that may lead to misdiagnosis of acute ST-segment elevation myocardial infarction (STEMI). This pseudo-STEMI may bring non-essential treatment. We aimed to confirm the ECG differences between HCM featured with pseudo-STEMI and acute STEMI.We retrospectively enrolled 59 HCM cases (Group A) and 56 acute STEMI cases (Group B). Based on the locations of STE, all the patients were divided into four subgroups, including HCM with STE in anterior leads (Group A1), anterior STEMI (Group B1), HCM with STE in inferior leads (Group A2) and inferior STEMI (Group B2). Several ECG parameters were compared between these subgroups.ECG parameters significantly differed between these groups, especially the number of leads with TWI. We evaluated the diagnostic value of ECG profiles for those groups. ROC analysis showed that for Group A vs. Group B, number of leads with TWI showed the highest AUC value of 0.805 and its cutoff of 2.5, with 76.3% sensitivity and 76.8% specificity. For Group A1 vs. Group B1, it showed the highest AUC value of 0.801 and its cut-off point was 2.5, with 77.1% sensitivity and 79.1% specificity. For Group A2 vs. Group B2, it showed the highest AUC value of 0.822 and the cut-off value was 4.5, with 54.5% sensitivity and 92.3% specificity.ECG plays a valid tool to distinguish "Pseudo-STEMI" HCM from acute STEMI, especially number of leads with TWI.

Idiopathic short stature (ISS) is the most common clinical cause of the short stature with an unclear aetiology and a lack of effective treatment. Circular RNAs have been shown to play a significant regulatory role through various signal transduction pathways in a variety of diseases in recent years. However, the role of circular RNAs on ISS is not yet well-understood and requires a special attention. The differentially expressed circular RNAs were screened by microarray chip analysis, and RT-qPCR was used to verify the expression of hsa_circ_0008870 in ISS patients. Subsequently, in vitro and in vivo experiments were conducted to determine the biological functions of hsa_circ_0008870 in ISS. The authors first confirmed that hsa_ circ_0008870 was downregulated in ISS children. Meanwhile, we also observed that the downregulated hsa_circ _0008870 significantly inhibited chondrocyte proliferation and endochondral ossification in vivo and in vitro. Mechanistically, hsa_circ_0008870 regulates MAPK1 expression by sponge miR-185-3p. This mechanism of action was further verified through rescue experiments. Finally, the authors revealed that the silencing of hsa_circ_0008870 induces low expression of MAPK1 by impairing the sponge action of miR-185-3p, thereby inhibiting chondrocyte proliferation, hypertrophy, and endochondral ossification, which results in a short stature phenotype. In addition to these, we also observed an interesting phenomenon that upregulated of miR-185-3p can in turn inhibit the expression of hsa_circ_0008870 in chondrocytes. This suggests that hsa_circ_0008870 could potentially serve as a therapeutic target for the treatment of ISS.

Objectives Idiopathic short stature (ISS), a disorder of unknown cause, accounts for approximately 80% of the clinical diagnoses of children with short stature. Exosomal circular RNA in plasma has been implicated in various disease processes. However, the role of exosome-derived circRNA in ISS has not been elucidated yet. Methods Plasma exosomes of ISS and normal children were cocultured with human chondrocytes. Microarray analysis and RT-PCR identified the differential expression of circRNA in exosomes between ISS and normal children. Hsa_circ_0063476 was upregulated or downregulated in human chondrocytes. Subsequently, overexpression rats of hsa_circ_0063476 was constructed via adenoviral vector to further validate the role of hsa_circ_0063476 on longitudinal bone growth via in vivo experiment. Results The plasma exosome of ISS children suppressed the expression of markers of chondrocyte hypertrophy and endochondral ossification. Subsequently, upregulation of hsa_circ_0063476 in ISS exosome was identified. In vitro experiments demonstrated that chondrocyte proliferation, cell cycle and endochondral ossification were suppressed, and apoptosis was increased following hsa_circ_0063476 overexpression in human chondrocytes. Conversely, silencing hsa_circ_0063476 in human chondrocytes can show opposite outcomes. Our study further revealed hsa_circ_0063476 overexpression in vitro can enhance chondrocyte apoptosis and inhibit the expression of markers of chondrocyte proliferation and endochondral ossification via miR-518c-3p/DDX6 axis. Additionally, the rats with hsa_circ_0063476 overexpression showed a short stature phenotype. Conclusions The authors identified a novel pathogenesis in ISS that exosome-derived hsa_circ_0063476 retards the expression of markers of endochondral ossification and impairs longitudinal bone growth via miR-518c-3p/DDX6 axis, which may provide a unique therapeutic avenue for ISS.

BackgroundDetermining risk factors of cardiovascular disease (CVD)-related mortality and evaluating their influence are important for effectively reducing corresponding mortality. However, few research findings have estimated the relationship between atrial fibrillation (AF) and CVD-related mortality among hypertension individuals.ObjectiveThe objective of this study was to investigate the epidemiology of AF in a hypertension population and determine the relationship between AF and CVD-related mortality.MethodsUsing a multistage, stratified, and cluster random sampling method, the prospective cohort study with a median follow-up of 3.51 years enrolled 10,678 hypertensive participants at baseline. The prevalence, awareness, and anticoagulation data of AF in this focal population were carefully assessed. Stepwise logistic regression and Cox regression analysis were respectively performed to evaluate the determinants of AF and the association between AF and CVD-related mortality.ResultsThe overall prevalence of AF was 1.3% (95% CI, 1.1%−1.6%) in the hypertensive population, and it was higher in men than in women (1.8% vs. 1.0%, respectively; p=0.001). The awareness of AF was 53.1%, and the rate of oral anticoagulant (OAC) therapy was only 4.2%, although all AF participants should have required according to the European Society of Cardiology guidelines. The determinants of AF included elder, male, and history of coronary heart disease in the hypertensive population. Besides, compared with individuals without AF, the risk of CVD-related mortality significantly increased in the hypertensive population with AF (HR 3.37, 95% CI 2.10–5.40).ConclusionOur results indicated a huge burden of AF and underuse of OAC therapy for them in a community-based hypertensive population. Considering that most of the risk factors of AF were unmodifiable in hypertensive individuals, as well as its high risk of mortality, long-term interventions including AF education, timely screening, and widespread use of OACs should be emphasized in the focal populations.

In this study, the effects of zymosan (HG, hydrolyzed glucan) on the structure and metabolism of fecal microbiota in Chinese healthy people was investigated by an in vitro simulated intestinal microecology fermentation model. We found that HG significantly regulated fecal microbiota composition, including the increase of Bifidobacterium, Faecalibacterium, Prevotella and the decrease of Escherichia-Shigella. Moreover, HG significantly increased the total production of short chain fatty acids (SCFAs) and gases, in which the production of Acetic acid, Propionic acid, CO2, and H2 significantly increased while the production of Isovaleric acid and NH3 significantly decreased. Additionally, the supplement of HG showed certain differences in the regulation of microbiota from four groups. HG significantly increased the relative abundance of Bifidobacterium and significantly decreased the relative abundance of Escherichia-Shigella excluding the older men group. Meanwhile, and the relative abundance of Lactobacillus was significantly increased in young populations. And the relative abundance of Bacteroides was significantly decreased only in the young women. Furthermore, HG significantly increased H2 concentration only in older men. These findings suggest that HG, as a new generation of prebiotics, could regulate the structure of fecal microbiota and its metabolites in a better direction, but when HG participates in precision nutrition formula, it may be necessary to consider the differences in the utilization of different populations.

ObjectivesTo evaluate the up-to-date epidemiology of diabetes in northeast China.MethodsThe cross-sectional study was conducted between September 2017 and March 2019 using a multistage, stratified and cluster random sampling method. 18 796 participants (28.9% urban and 71.1% rural) aged ≥40 years were enrolled. Diabetes and pre-diabetes were diagnosed according to the history, fasting plasma glucose (FPG) and glycosylated haemoglobin A1c (HbA1c) levels.ResultsThe prevalence of diabetes was 17.1%, higher in urban than in rural residents (20.2% vs 15.8%, pConclusionA considerable burden of diabetes was observed in northeast China, with high percentage of untreated diabetes, high prevalence of pre-diabetes, high overall FPG level and multiple uncontrolled risk factors in patients with diabetics. Therefore, region-specific strategies on prevention and management of diabetes should be emphasised.

Glucose-responsive insulin delivery systems show great promise to improve therapeutic outcomes and quality of life for people with diabetes. Herein, a new microneedle-array patch containing pH-sensitive insulin-loaded nanoparticles (NPs) (SNP(I)) together with glucose oxidase (GOx)- and catalase (CAT)-loaded pH-insensitive NPs (iSNP(G+C)) is constructed for transcutaneous glucose-responsive insulin delivery. SNP(I) are prepared via double emulsion from a pH-sensitive amphiphilic block copolymer, and undergo rapid dissociation to promote insulin release at a mild acidic environment induced by GOx in iSNP(G+C) under hyperglycemic conditions. CAT in iSNP(G+C) can further consume excess H2O2 generated during GOx oxidation, and thus reduce the risk of inflammation toward the normal skin. The in vivo study on type 1 diabetic mice demonstrates that the platform can effectively regulate blood glucose levels within normal ranges for a prolonged period.

Background and Aims TRIM21 is a ubiquitin E3 ligase that is implicated in numerous biological processes including immune response, cell metabolism, redox homeostasis, and cancer development. We recently reported that TRIM21 can negatively regulate the p62-Keap1-Nrf2 antioxidant pathway by ubiquitylating p62 and prevents its oligomerization and protein sequestration function. As redox homeostasis plays a pivotal role in many cancers including liver cancer, we sought to determine the role of TRIM21 in hepatocarcinogenesis. Methods We examined the correlation between TRIM21 expression and the disease using publicly available data sets and 49 cases of HCC clinical samples. We used TRIM21 genetic knockout mice to determine how TRIM21 ablation impact HCC induced by the carcinogen DEN plus phenobarbital (PB). We explored the mechanism that loss of TRIM21 protects cells from DEN-induced oxidative damage and cell death. Results There is a positive correlation between TRIM21 expression and HCC. Consistently, TRIM21-knockout mice are resistant to DEN-induced hepatocarcinogenesis. This is accompanied by decreased cell death and tissue damage upon DEN treatment, hence reduced hepatic tissue repair response and compensatory proliferation. Cells deficient in TRIM21 display enhanced p62 sequestration of Keap1 and are protected from DEN-induced ROS induction and cell death. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient mutant TRIM21 impedes the protection from DEN-induced oxidative damage and cell death in TRIM21-deficient cells. Conclusions Increased TRIM21 expression is associated with human HCC. Genetic ablation of TRIM21 leads to protection against oxidative hepatic damage and decreased hepatocarcinogenesis, suggesting TRIM21 as a preventive and therapeutic target.

A nonincreasing sequence π = (d1,…,dn) of nonnegative integers is a graphic sequence if it is realizable by a simple graph G on n vertices. In this case, G is referred to as a realization of π. Given a graph H, a graphic sequence π is potentially H-graphic if π has a realization containing H as a subgraph. For graphs G1 and G2, the potential-Ramsey number rpot(G1, G2) is the smallest integer k such that for every k-term graphic sequence π, either π is potentially G1-graphic or the complementary sequence $$\overline \pi = \left({k - 1 - {d_k}, \cdots k - 1 - {d_1}} \right)$$ is potentially G2-graphic. For $$0 \le k \le \left\lfloor {{t \over 2}} \right\rfloor $$ , denote $$K_t^{- k}$$ to be the graph obtained from Kt by deleting k independent edges. If k = 0, Busch et al. (Graphs Combin., 30(2014)847–859) present a lower bound on rpot(G, Kt) by using the 1-dependence number of G. In this paper, we utilize i-dependence number of G for i ≥ 1 to give a new lower bound on rpot(G, $$K_t^{- k}$$ ) for any k with $$0 \le k \le \left\lfloor {{t \over 2}} \right\rfloor $$ . Moreover, we also determine the exact values of rpot(Kn, $$K_t^{- k}$$ ) for 1 ≤ k ≤ 2.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Sorafenib (sfb) is widely used in clinics for advanced HCC therapy. However, the therapeutic efficacy of sfb is suboptimal due to its poor water solubility, low bioavailability, and side effects. Here, we employed a clinically safe polymer poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to prepare a nanoparticle (NP)-based sfb formulation (NP-sfb) and tested its antitumor effect in multiple HCC models. NP-sfb could achieve effective drug loading and remain stable under physiological conditions. NP-sfb could be taken up by HepG2, Hepa1-6, and H22 cells and could efficiently inhibit cell proliferation and/or promote cell apoptosis. In vivo studies indicated that NP-sfb showed significantly improved therapeutic efficacy compared with free-sfb at the same dose or even higher doses. Mechanistic studies demonstrated that NP-sfb not only inhibited tumor proliferation and angiogenesis but also stimulated the tumor microenvironment by reducing the infiltration of immunosuppressive myeloid cells and increasing the ratio of cytotoxic T cells. This study demonstrates that the NP-based formulation is a promising strategy to improve the clinical application of sfb.

Summary Background and aims Immune response against hepatitis B virus (HBV) infection is an important risk factor for the development of hepatocellular carcinoma (HCC). Studies have reported that interleukin 22 (IL-22) exhibits both protective and pathological properties in liver diseases. Our aim was to explore the importance of IL-22 in the development of HCC, and to characterize the relationship between IL-22 levels and the prognosis of HCC. Methods Totally, 136 liver biopsy specimens from 46 patients with chronic hepatitis B (CHB), 37 with atypical hyperplasia (AH), 53 with HCC, patient-matched tumors and peritumoral surgical specimens from 56 HCC patients included in the study. The expression of IL-22 and CD8 was evaluated by immunochemistry. Corresponding serum samples were collected from 30 CHB, 30 AH, and 30 HCC patients. IL-22 expression was determined by an enzyme linked immunosorbent assay. Results Liver-infiltrating IL-22+ cells increased in a stepwise manner from CHB to AH and HCC (CHB vs. AH, P = 0.002; AH vs. HCC, P = 0.010), whereas a decreasing trend was observed for CD8+ T cells (CHB vs. AH, P = 0.031; AH vs. HCC, P = 0.652). Serum IL-22 levels also increased from CHB to AH and HCC (CHB vs. AH, P = 0.024; AH vs. HCC, P = 0.026). Tumor-infiltrating IL-22+ cells and serum IL-22 were associated with histologic grade (P = 0.024 and P = 0.033). Additionally, CD8+ T cells correlated with tumor size (P = 0.032). Furthermore, the high intratumoral IL-22+ cell group and high serum IL-22 group showed lower overall survival (OS; P = 0.001, P = 0.017) and disease-free survival (DFS; P = 0.005, P Conclusions These findings indicate that IL-22 promotes the progression of HCC in CHB patients. High tumor-infiltrating IL-22+ cells and serum IL-22 levels are thought to be unfavorable prognostic indicators for HCC.

The reaction of terpyridine derivatives L1/L2 with Ln(NO3)3 led to the formation of three new mononuclear complexes with formulae [LnL1(CH3OH)(H2O)(NO3)2]NO3•2CH3OH (Ln=Yb, 1 ; Ln=Dy, 2 ) and [DyL2(NO3)3(H2O)]•2CH3OH ( 3 ). Complexes 1 , 2 and 3 were characterized by crystal structure determination, magnetic properties study. Ac magnetic susceptibility measurements reveal that all complexes exhibited field-induced single-ion magnet (SIM) behavior.

Polymeric micelles hold great potential for anticancer drug delivery. Sufficient integrity of polymeric micelles after intravenous injection is critical for successful drug delivery to solid tumors, but accurate measurement of the in vivo micellar integrity remains challenging. Methods based on Forster resonance energy transfer (FRET) to monitor the in vivo micellar integrity are frequently used. However, the self-quenching effect of these FRET fluorophores used has been improperly ignored and has caused inaccurate measurements. Herein, we report a FRET-based approach using the large Stokes shift (LSS) fluorophores NBD-X and MS735 as the donor and acceptor, respectively, to investigate the integrity of polyethylene glycol-block-poly(e-caprolactone) (PEG-PCL) micelles. We established a mathematical formula for the integrity calculation, and an in vitro verification experiment showed that the formula results exactly matched the simulated results. Our results demonstrated that PEG-PCL micelles gradually dissociated in blood circulation, but approximately 60% of the micelles in plasma remained intact 72 h after intravenous (i.v.) injection. This LSS fluorophore-based FRET approach can be used to accurately monitor the integrity of nanoparticles, and this study demonstrates that most of PEG-PCL micelles maintain their aggregation state during blood circulation for anticancer drug delivery.

Summary Targeted bioorthogonal catalysis holds great potential for localized prodrug activation. Although enantiomerically pure drugs are of vital importance in the clinic, chiral drug synthesis by bioorthogonal reactions in living systems is scarcely reported. Toward this goal, we constructed chirally modified Pd catalysts for the asymmetric transfer hydrogenation (ATH) reaction by using sodium formate as the biocompatible reductant. By combining the ATH reaction and chemotaxis of neutrophil membrane, we achieved inflammation site-selective chiral drug synthesis in living cells. As a proof of concept, we synthesized the chiral model drug ibuprofen in situ by a targeted ATH reaction to alleviate inflammation in the mouse paw as an in vivo model. Compared with controls, the neutrophil-membrane-coated chiral Pd catalysts exhibited inflammation-targeted capability and enantioselectivity simultaneously in the anti-inflammatory action. This study could offer a novel perspective for bioorthogonal catalysis in targeted prodrug activation.

Background Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indices is the best to predict CVD in hypertensive people. Methods Northeast China Rural Cardiovascular Health Study (NCRCHS) is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013 to 2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip (WHR)and body mass index (BMI) were calculated and analyzed in relation to the CVD incidence. Results A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35–92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). Conclusion These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR can be used to predict CVD incidence in hypertensive adults.

The interplay between a dS black hole and cosmological horizons introduces distinctive thermodynamic behavior in a dS spacetime (for example the well-known upper bounds of mass and entropy in Class. Quant. Grav. 37 (2020) 5). Based on this point, we present the Hawking-Page (HP) phase transition of the four-dimensional dS spacetime with non-linear charge correction when the effective pressure is fixed, and analyze the effects of different effective pressures and non-linear charge corrections on HP phase transition. The evolution of this dS spacetime undergoing the HP phase transition is also investigated. We find that the existent curve of HP phase transition is a closed one with two different branches. That means there exist the upper bounds of the HP temperature and HP pressure, which is completely distinguished with that in AdS spacetime. And with the decreasing of the distance between two horizons, the dS spacetime at the coexistent curve of HP phase transition is going along with different branches. Furthermore we also explore the influence of charge and non-linear charge correction on the coexistent curve.

The development of chemoresistance is a major hurdle for the treatment of colorectal cancer (CRC), which contributes remarkably to the poor clinical prognosis. Nanodrug delivery systems show great potential in overcoming chemoresistance, but limited by the lack of identification of chemoresistance targets from cancer patients. In the present study, we enrolled chemotherapy-resistant or sensitive CRC patients and used the next-generation RNA sequencing to reveal that Asporin (ASPN) is highly expressed in tumor tissues from oxaliplatin (OXA)-resistant patients and closely correlated with a poor prognosis of CRC. Downregulation of ASPN reversed OXA resistance and promoted cell apoptosis both in vitro and in vivo. To overcome ASPN-mediated OXA resistance, we constructed a nanoparticle-based co-delivery system (denoted as PPO-siASPN) for simultaneous delivery of OXA and siRNA targeting ASPN (siASPN). PPO-siASPN not only facilitated the intracellular delivery of OXA through the enhanced cellular uptake, but effectively suppressed ASPN expression for synergistic antitumor activity in vitro and in vivo. In the more clinically relevant patient-derived xenograft (PDX) mouse model, systemic administration of PPO-siASPN achieved a remarkable therapeutic effect. This study uncovered the critical role of ASPN in causing OXA resistance in CRC patients and suggests a promising nanoformulation that may be more effective than current standard-of-care medications.

In this study, the effects of zymosan (HG, hydrolyzed glucan) on the structure and metabolism of fecal microbiota in Chinese healthy people was investigated by an

Cytochrome c (Cyt c) is an important, multifunctional protein for controlling cell fate. Emerging evidence suggests a potential role of Cyt c in the amyloid pathology associated with Alzheimer’s disease (AD); however, the interaction between Cyt c and Abeta with the consequent impact on the aggregation and toxicity of Abeta is not known. Here we report the discovery that Cyt c can directly bind to Abeta and alter the aggregation and toxicity profiles of Abeta in a peroxide-dependent manner. Cyt c redirects Abeta peptides into less toxic, off-pathway amorphous aggregates in the presence of hydrogen peroxide (H2O2), whereas it accelerates Abeta fibrillization without H2O2. Such effects can be achieved by three possible mechanisms, including the complexation between Cyt c and Abeta, the oxidation of Abeta by Cyt c and H2O2, and the H2O2-mediated modification of Cyt c. Our studies demonstrate a new function of Cyt c as a modulator against Abeta amyloidogenesis.

Long-term hypercaloric diets may adversely affect the development of ovarian follicles. We investigated the effects of high sugar (HS), high fat low sugar (HFLS), and high fat normal sugar (HFNS) diets on the ovarian follicle development in mice fed with these diets as compared to those fed with normal diet (control) for 180 days. Body weight, gonadal fat, glucose, lipid, insulin, estrous cycle, sex hormones and ovarian tissues were examined, and metabolism-related protein expression in the ovaries was evaluated by immunoblotting. The mice fed with hypercaloric diets showed hyperinsulinemia and hyperlipidemia, and exhibited heavier body and gonadal fat weights, longer estrous cycles, and fewer preantral and antral follicles than mice fed with normal diet. The sex hormone levels in the blood were similar to those in controls, except for significantly elevated estradiol levels in the HS diet group. The AMPKα phosphorylation was reduced, while AKT phosphorylation and caspase-3 levels were increased in the ovarian tissues of mice in all three hypercaloric diet groups than those in control. Taken together, the results suggest hyperinsulinemia and hyperlipidemia as possible mechanisms that impair the development of ovarian follicles in response to long-term exposure to unhealthy hypercaloric diets.

Dendrobium officinale Kimura et Migo, one of the most important orchids because of its medicinal and edible value, has a typical Dendrobium Sw. flora scent, which has great application potential and commercial value to be characterized. The aroma-active compounds originating from D. officinale fresh flowers (DFF) were investigated using a sensomics approach. A combined solid phase microextraction and solvent-assisted flavor evaporation method were used to accurately capture the overall aromatic profile. Exactly 34 odorants were detected and identified by aroma extract dilution analysis (AEDA) coupled with gas chromatography/olfactometry-mass spectrometry (GC/O-MS) in DFF, of which nine odorants had a flavor dilution (FD) factor ≥27. All 34 odorants were further quantified. The odor activity values (OAVs) were calculated with the highest value of 7444, in which 18 compounds were confirmed to be key odorants, including 1-octen-3-ol, hexanal, nonanal, phenylacetaldehyde, linalool, 4-oxoisophorone, theaspirane, methyl salicylate, etc. Among the studies above, 42 out of 78 volatiles and 14 out of 34 odorants were identified in DFF for the first time. Then, the aroma profile of the DFF was simulated successfully by aroma recombination experiments based on the quantitation results, and the omission test suggested that alcohols are the decisive type of compounds in the DFF key odorants. In addition, a progressive addition test showed that the aroma recombinate prepared with 18 reference key odorants was able to reconstruct the characteristic aroma of DFF. In comparison, the recombinate constituted by mixing all 34 reference odorants in the same concentrations as determined in the DDF sample could mimic the flower scent and closely match the sensory attributes of the original D. officinale fresh flower.

In this paper, thermodynamic properties of the Reissner-Nordström-de Sitter (RN-dS) black hole have been studied on the basis of the correlation between the black hole and cosmological horizons. It is found that the RN-dS black hole experiences a phase transition, when its state parameters satisfy certain conditions. From the analysis of the interaction between two horizons in RN-dS spacetime, we get the numerical solution of the interaction between two horizons. It makes us to realize the force between the black hole and cosmological horizons, which can be regarded as a candidate to explain our accelerating expansion universe. That provides a new window to explore the physical mechanism of the cosmic accelerating expansion.

Hydrogel as a local drug depot can increase drug concentration at the tumor site. However, conventional drug-loaded hydrogel is typically formed by direct dissolution of drug molecules inside the hydrogel, which usually suffers from limited drug retention and poor tumor penetration. In this study, a nanocomposite hydrogel consisting of oxaliplatin (OXA)-conjugated G5 polyamidoamine (G5-OXA) and oxidized dextran (Dex-CHO) is constructed to improve local drug delivery. The OXA-containing nanocomposite hydrogel (denoted as PDO gel) is injectable and could maintain in vivo up to more than three weeks, which increases drug retention in tumor tissues. More interestingly, G5-OXA released from the PDO gel show potent tumor penetration mainly through an active transcytosis process. In vivo antitumor studies in an orthotopic 4T1 tumor model show that PDO gel significantly inhibits primary tumor growth as well as the metastasis. In addition, the PDO gel can also activate the immunosuppressive tumor microenvironment through immunogenic cell death effect, and further improves therapeutic efficacy with the combination of PD-1 antibody. These results demonstrate that the nanocomposite hydrogel can simultaneously enhance the retention and penetration of chemotherapeutic drugs via the combination of both advantages of hydrogel and nanoparticles, which provides new insights for the design of local drug delivery systems. STATEMENT OF SIGNIFICANCE: Hydrogel represents an important class of local drug delivery depot. However, conventional drug-loaded hydrogel is usually achieved by direct dissolution of small drug molecules inside the hydrogel, which typically suffers from limited drug retention and poor tumor penetration. Herein, we developed a nanocomposite hydrogel, which could gradually degrade and release drug-conjugated small nanoparticles (∼ 6 nm) for improved tumor penetration through the combination of an active transcytosis process and a passive diffusion process. This nanocomposite hydrogel system improved tumor penetration and retention of drug in primary tumors as well as the drug deposition in lymph nodes, which significantly suppressed tumor growth and metastasis.

To explore the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in patients with primary bone marrow lymphoma.The clinical data of 23 patients with primary bone marrow lymphoma diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 were collected. The characteristics of bone marrow aspiration, bone marrow biopsy and immunohistochemistry results were analyzed retrospectively, and the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in primary bone marrow lymphoma were clarified.Most of primary bone marrow lymphoma was B-cell lymphoma, among which diffuse large B-cell lymphoma was the most common pathological type. Typical lymphoma cells could be found in all the patients. 78.26% of the patients could be diagnosed as lymphoma with pathological type, while 91.30% were diagnosed as lymphoma through combined with the bone marrow immunohistochemistry.Bone marrow cell morphology combined with immunohistochemistry shows very important diagnostic value in patients with primary bone marrow lymphoma.骨髓细胞形态学联合原位免疫组化在原发骨髓淋巴瘤患者中的诊断价值.探讨骨髓细胞形态学联合原位免疫组化在原发骨髓淋巴瘤患者中的诊断价值。.收集西安交通大学医学院第一附属医院2010年1月- 2019年12月23例确诊的原发骨髓淋巴瘤患者的临床资料，回顾性分析骨髓细胞形态学、原位免疫组化和免疫分型等的特点，明确骨髓细胞形态学联合原位免疫组化在原发骨髓淋巴瘤中的诊断价值。.原发骨髓淋巴瘤以B细胞淋巴瘤为主，其中弥漫大B细胞淋巴瘤为最常见的病理类型；所有患者骨髓均可见典型的淋巴瘤细胞，联合原位免疫组化78.26%的患者能够被诊断为原发骨髓淋巴瘤，91.30%的患者确诊为淋巴瘤。.骨髓细胞形态学联合原位免疫组化在原发骨髓淋巴瘤患者中具有重要诊断价值。.