Preliminary investigation and analysis of nucleotide site variability of nine glycoproteins on varicella-zoster virus envelope, Jilin Province, China, 2010-March 2024.

Varicella is endemic worldwide. In China, varicella has not yet been included in the list of legal infectious diseases, nor has a unified national surveillance program been established. And the live attenuated varicella vaccine has not been included in routine immunization. In this study, we analyzed for the first time the varicella epidemiology in Jilin Province in the past 20 years, and the nucleotide site, amino acid site and N-glycosylation site variation of glycoprotein in varicella-zoster virus (VZV) surface 9 in the past 15 years. The results showed that the reported incidence of varicella in Jilin Province in the last 20 years was fluctuating above and below 20/100,000, especially after the epidemic of the COVID-19, and fatal cases appeared in individual years. The genotypic branching of VZV was monitored as Clade 2 in the last 15 years. 9 glycogen nucleotide sites of VZV had different degrees of variability, and the variability had specificity. Therefore, it gives us the idea that in order to reduce the incidence of varicella and herpes zoster, a provincial or even national surveillance program should be introduced as early as possible, and the dynamic monitoring of the variability of the nucleotide sites of VZV should be strengthened at the same time as the vaccine immunization strategy is introduced.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Mechanism of Porphyra Yezoensis Polysaccharides in Inhibiting Hyperoxalate-Induced Renal Injury and Crystal Deposition.

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.

Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.

A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat. In enzymatic assays, compound 3b, containing a 2-acyliminobenzimidazole moiety and hydroxamic acid side chain, could inhibit both ALK and HDAC6 (IC50 = 16 nM and 1.03 µM, respectively). Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM). Moreover, 3b inhibited the proliferation of several cancer cell lines, including ALK-addicted H2228 cells. To evaluate its potential for treating cancers in vivo, 3b was used in a human A549 xenograft model with BALB/c nude mice. At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin-induced apoptosis in castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti-CRPC strategy. METHODS: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay and anchorage-dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell-cycle progression. Cell-based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis. RESULTS: A total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC50, 3.5 nM in enzyme assay; IC50, 1.0 µM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC50, 5.4 µM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α-tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl-2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin-induced cell death through impairment of cisplatin-evoked DNA damage response and DNA repair in both ATR-Chk1 and ATM-Chk2 pathways. CONCLUSION: The data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin-induced cell apoptosis through impeding DNA damage repair pathways.

J24335 exerts neuroprotective effects against 6-hydroxydopamine-induced lesions in PC12 cells and mice.

Parkinson's disease is the second most prevalent age-related neurodegenerative disease and disrupts the lives of people aged >60 years. Meanwhile, single-target drugs becoming inapplicable as PD pathogenesis diversifies. Mitochondrial dysfunction and neurotoxicity have been shown to be relevant to the pathogenesis of PD. The novel synthetic compound J24335 (11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime), which has been researched similarly to J2326, has the potential to be a multi-targeted drug and alleviate these lesions. Therefore, we investigated the mechanism of action and potential neuroprotective function of J24335 against 6-OHDA-induced neurotoxicity in mice, and in PC12 cell models. The key target of action of J24335 was also screened. MTT assay, LDH assay, flow cytometry, RT-PCR, LC-MS, OCR and ECAR detection, and Western Blot analysis were performed to characterize the neuroprotective effects of J24335 on PC12 cells and its potential mechanism. Behavioral tests and immunohistochemistry were used to evaluate behavioral changes and brain lesions in mice. Moreover, bioinformatics was employed to assess the drug-likeness of J24335 and screen its potential targets. J24335 attenuated the degradation of mitochondrial membrane potential and enhanced glucose metabolism and mitochondrial biosynthesis to ameliorate 6-OHDA-induced mitochondrial dysfunction. Animal behavioral tests demonstrated that J24335 markedly improved motor function and loss of TH-positive neurons and dopaminergic nerve fibers, and contributed to an increase in the levels of dopamine and its metabolites in brain tissue. The activation of both the CREB/PGC-1α/NRF-1/TFAM and PKA/Akt/GSK-3ß pathways was a major contributor to the neuroprotective effects of J24335. Furthermore, bioinformatics predictions revealed that J24335 is a low toxicity and highly BBB permeable compound targeting 8 key genes (SRC, EGFR, ERBB2, SYK, MAPK14, LYN, NTRK1 and PTPN1). Molecular docking suggested a strong and stable binding between J24335 and the 8 core targets. Taken together, our results indicated that J24335, as a multi-targeted neuroprotective agent with promising therapeutic potential for PD, could protect against 6-OHDA-induced neurotoxicity via two potential pathways in mice and PC12 cells.

Effect of aerobic exercise on glycolipid metabolism,skeletal muscle inflammation and autophagy in type 2 diabetic rats / 中国组织工程研究

BACKGROUND:Obesity and its relevant chronic inflammation are important risk factors for inducing type 2 diabetes.This inflammatory response will further involve skeletal muscle,leading to an increase in catabolic and autophagic fluxes in skeletal muscle.Aerobic exercise is the mainstream mode of exercise in the prevention and treatment of type 2 diabetes,and may also has a certain protective effect on skeletal muscle. OBJECTIVE:To explore the effects and regulatory mechanisms of aerobic exercise on glucolipid metabolism,skeletal muscle inflammation and autophagy in type 2 diabetic rats. METHODS:Animal models of type 2 diabetes were established in rats by 8-week high-fat feeding combined with streptozotocin injection,and the experimental rats were then divided into normal control group,normal exercise group,diabetic control group and diabetic exercise group.The exercise group performed 4 weeks of aerobic exercise(16 m/min,60 min/d,5 d/wk).The levels of blood glucose,high-density lipoprotein,low-density lipoprotein and triglyceride in serum were measured by an automated biochemical analyzer.Serum insulin level was determined using enzyme-linked immunosorbent assay and the insulin resistance index and area under the glucose metabolism curve were calculated.The levels of interleukin 6 and tumor necrosis factor α in skeletal muscle were measured by enzyme-linked immunosorbent assay after 4 weeks of aerobic exercise,and the expression levels of forkhead box protein O3(FoxO3),LC3 and p62 in skeletal muscle were measured by western blot assay. RESULTS AND CONCLUSION:The area under the glucose tolerance curve and insulin resistance index both increased significantly in type 2 diabetic rats(P<0.001,P=0.025),and aerobic exercise significantly reduced the area under the glucose tolerance curve and insulin resistance index in the normal exercise group(P<0.001,P=0.038)and diabetic exercise group(P<0.001,P=0.004).Serum high-density lipoprotein significantly decreased(P=0.030),and low-density lipoprotein and triglyceride(P=0.027,P=0.014)levels significantly increased in the diabetic control group compared with the normal control group.Aerobic exercise significantly reduced triglyceride and low-density lipoprotein levels in the normal exercise group(P=0.019,P=0.008)as well as triglyceride levels in the diabetic exercise group(P=0.022).Both interleukin-6 and tumor necrosis factor α levels were significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group(P<0.001,P=0.007),and aerobic exercise significantly reduced tumor necrosis factor α levels in the diabetic exercise group(P=0.017).The LC3-Ⅱ/LC3-I was significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group.Aerobic exercise significantly increased the LC3-Ⅱ/LC3-I in the normal exercise group(P<0.001)and decreased the LC3-Ⅱ/LC3-I,FoxO3 and p62 protein expression levels in the diabetic exercise group(P=0.026,P=0.050,P=0.048).To conclusion,type 2 diabetes model established by high-fat feeding combined with streptozotocin injection has obvious glycolipid metabolism disorder,and leads to inflammatory response and excessive activation of autophagy in skeletal muscle.Aerobic exercise can improve glycolipid metabolism,reduce local inflammation in skeletal muscle and inhibit autophagy,and finally play a protective role in skeletal muscle.

A cross-sectional survey on the prevalence and risk factors of sarcopenia in the elderly in some areas of the Yunnan-Guizhou Plateau / 中国组织工程研究

BACKGROUND:Epidemiological research data on sarcopenia in China are concentrated in some provincial capitals and developed areas,while research on sarcopenia in the elderly in the Yunnan-Guizhou Plateau is at the initial stage,and there is still a lack of understanding of the development mechanism,influencing factors and prevention methods of sarcopenia. OBJECTIVE:Based on the 2019 Asian Sarcopenia Working Group Standard(AWGS2019),to assess sarcopenia in the elderly in the Yunnan-Guizhou Plateau,while analyzing the prevalence and risk factors of sarcopenia in the elderly. METHODS:A total of 1 327 elderly study subjects(650 males and 677 females)were recruited and their socio-demographic characteristics,clinical data and physical activity levels were collected.The prevalence of sarcopenia was screened using the AWGS2019 criteria.The possible influencing factors for sarcopenia were screened by univariate analysis,including χ2 test for comparing count data and t-test for comparing measurement data,and the indicators through univariate screening were included in the binary logistic regression model to assess the risk factors for sarcopenia,and then the odds ratio(OR)and 95%confidence interval(CI)were calculated. RESULTS AND CONCLUSION:The prevalence of sarcopenia in the elderly in the Yunnan-Guizhou Plateau was 14.62%(12.73%male and 16.49%female).Aging(OR=1.158,95%CI:1.133-1.185),female(OR=2.416,95%CI:1.629-3.586),fasting blood glucose≥7.0 mmol/L(OR=1.653,95%CI:1.071-2.551),smoking(OR=1.595,95%CI:1.043-2.438)and a low physical activity level(OR=1.778,95%CI:1.154-2.737)were all independent risk factors for sarcopenia,while body mass index was a protective factor for sarcopenia(OR=0.708,95%CI:0.583-0.859).These findings indicate that aging,female,fasting glucose≥7.0 mmol/L,smoking and low physical activity levels all increase the risk of sarcopenia,while increased body mass index can decrease the risk of sarcopenia.To conclude,the elderly(especially women)should maintain a healthy lifestyle and slightly higher body mass index levels during the aging process,thus reducing the risk of sarcopenia.

Mode of Interdisciplinary Research of Traditional Chinese Medicine： Learn from the Study of Biological Characteristics and Mathematical Representation of the Transformation from Phlegm-Dampness Constitution to Dyslipidemia / 中医杂志

The current interdisciplinary research on traditional Chinese medicine （TCM） often comes from the simple combination of TCM application needs and mature engineering technology. Actually， higher goal of cross-disciplinary research should be the win-win development of TCM and interdisciplinary majors. In detail， to enhance the innovative development of original thinking mode of TCM， meanwhile， to stimulate the innovation of interdisciplinary majors with medical tasks. Previously， we successfully performed the research on the objective representation of pre-disease and disease state of dyslipidemia in population with phlegm-dampness constitution. Taking this project as an example， this paper discusses the methodology on scientific issue positioning， key medical tasks selection， interdisciplinary theory， and technology exploration， to expounds the research design and ideas which could be generalized in other cross-disciplinary research of TCM.

The Correlation between Blood Stasis Constitution and Diseases： A Bibliometric Analysis of 135 Clinical Studies / 中医杂志

ObjectiveTo explore the correlation between blood stasis constitution （BSC） and diseases based on constitution literature involving “constitution-diseases correlation”. MethodsA comprehensive search was conducted on six Chinese and English electronic databases including CNKI， Wanfang， VIP， SinoMed， PubMed and Embase to find all clinical researches on the correlation between constitution and diseases using the Classification and Identification of Chinese Medicine Constitution standard from April 1st， 2009 to December 31st， 2022， and the participants of the research were BSC related. By analyzing the characteristics of the literature， such as authors， publication institutes， participants， and results， the disease with the highest proportion of BSC distribution or BSC as their risk factors or protective factors were summarized to explore the correlation between BSC and diseases. ResultsTotally 135 clinical studies on diseases highly related to BSC were included， with a total sample size of 71 172 cases.There were 27 keywords in the articles appeared more than 3 times， including the elderly， lumbar disc herniation， coronary heart disease， cardiovascular disease， and endometriosis. In the author's clustering， included studis were mainly from Shenzhen Hospital of Beijing University of Chinese Medicine， Second Affiliated Hospital of Guangzhou University of Chinese Medicine， and Wenzhou Central Hospital. In terms of blood stasis related diseases， 81 studies showed that BSC was the most common type of constitution in the study population， involving 48 disease or morbid states. The diseases and median proportions of BSC with reported literature ≥3 included coronary heart disease （28.8%）， endometriosis （31.3%）， neurocognitive impairment （26.4%）， lumbar disc herniation （26.0%）， ischemic stroke （25.0%）， adenomyosis （34.7%）， and endometrial polyps （25.0%）. Fifty-eight studies found that BSC was a risk factor for disease occurrence，and these diseases reported more than 3 times included hypertension （median OR = 2.956）， type 2 diabetes （median OR = 3.436），osteoporosis （median OR = 5.171）， sudden deafness （median OR = 3.827） and endometriosis （median OR = 5.412）. One study indicated BSC as the protective factor of lateral growth tumor of large intestine （median OR = 0.161）. ConclusionBSC is closely related to circulatory system diseases， urogenital system diseases， and musculoskeletal system diseases.

The construction and its implication of the cancer life-cycle prevention and control system in Japan / 中国卫生政策研究

As the country with the largest number of new cancer cases and deaths,China faces a serious situation with a large cancer population base,low relative survival rate,and low adherence to cancer screening.Neighboring Japan,which has the longest life expectancy in the world,has a much higher relative survival rate than China,despite having a similarly high cancer rate,due to its well-established system of cancer prevention and control.Being an Asian country,the major prevalent cancers in China and Japan are similar in spectrum and can be referred to more.This article introduces the construction of Japan's cancer life-cycle prevention and control system of"cancer prevention","cancer care",and"coexistence with cancer"starting from the three major goals of Japan's cancer prevention and control program,and focuses on the improvement of cancer screening in Japan and the improvement of cancer survival in China.It also highlights the means and methods used to increase the cancer screening rate in Japan,with a view to providing suggestions for cancer prevention and control in China.

Traditional Chinese Medicine constitution among patients with allergic rhinitis and its correlation with anxiety and depression.

OBJECTIVE: To preliminary investigate the distribution of Traditional Chinese Medicine (TCM) constitution among patients with allergic rhinitis (AR) and reveal the related factors with anxiety and depression. METHODS: Between July 2020 and June 2021, specialist doctor recruited AR patients in Beijing and Shanghai. A total of 630 patients admitted to participate in the survey, and 516 (81.9%) (male 54.3%, female 45.7%) participants completed the questionnaires. Three scales including Constitution in Chinese Medicine Questionnaire (CCMQ), Generalized Anxiety Disorder Questionnaire (GAD-7) and The Patient Health Queationaire-9 (PHQ-9) were applied. The χ2 and the Fisher's exact test were used to evaluate the classification data, multivariate logistic regression was used to explore the related factors of anxiety and depression. RESULTS: According to 516 AR patients, the most commonly first-constitution was Yang-deficiency (22.1%) and frequent of all constitutions was inherited-special (21.6%). One third of AR patients (33.5%) suffered from anxiety, nearly half of AR patients (46.5%) were found to be depressive. Inherited-special (27.7%) was the most common constitution in patients with anxiety whereas Yang-deficiency (26.7%) was most common constitution in patients with depression. Sex, duration of symptoms, balanced, Qi-deficiency, phlegm-dampness, Qi-stagnation, and inherited-special constitutions were related with anxiety; Sex, income, duration of symptoms, balanced, Qi-deficiency, Yang-deficiency, phlegm-dampness, Qi-stagnation, and inherited-special constitutions were related with depression. CONCLUSIONS: According to our study, the commonly constitution types of AR were Yang-deficiency and inherited-special. We found that the prevalence value of anxiety and depression were high. People with Qi-deficiency, phlegm-dampness, Qi-stagnation, and inherited-special constitutions were more likely to have mental problems than the others. Controlling these influential factors might be beneficial for clinical health management of AR patients, and the government should apply appropriate mental health treatment services to offer psychiatric support.

Antagonizing pathological α-synuclein-mediated neurodegeneration by J24335 via the activation of immunoproteasome.

The aggregation of misfolded proteins, such as α-synuclein in Parkinson's disease (PD), occurs intracellularly or extracellularly in the majority of neurodegenerative diseases. The immunoproteasome has more potent chymotrypsin-like activity than normal proteasome. Thus, degradation of α-synuclein aggregation via immunoproteasome is an attractive approach for PD drug development. Herein, we aimed to determine if novel compound, 11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime (named as J24335), is a promising candidate for disease-modifying therapy to prevent the pathological progression of neurodegenerative diseases, such as PD. The effects of J24335 on inducible PC12/A53T-α-syn cell viability and cytotoxicity were evaluated by MTT assay and LDH assay, respectively. Evaluation of various proteasome activities was done by measuring the luminescence of enzymatic activity after the addition of different amounts of aminoluciferin. Immunoblotting and real-time PCR were employed to detect the expression of various proteins and genes, respectively. We also used a transgenic mouse model for behavioral testing and immunochemical analysis, to assess the neuroprotective effects of J24335. J24335 inhibited wild-type and mutant α-synuclein aggregation without affecting the growth or death of neuronal cells. The inhibition of α-synuclein aggregation by J24335 was caused by activation of immunoproteasome, as mediated by upregulation of LMP7, and increased cellular chymotrypsin-like activity in 20S proteasome. J24335-enhanced immunoproteasome activity was mediated by PKA/Akt/mTOR pathway activation. Moreover, animal studies revealed that J24335 treatment markedly mitigated both the loss of tyrosine hydroxylase-positive (TH-) neurons and impaired motor skill development. This is the first report to use J24335 as an immunoproteasome enhancing agent to antagonize pathological α-synuclein-mediated neurodegeneration.

Discovery of HDAC6, HDAC8, and 6/8 Inhibitors and Development of Cell-Based Drug Screening Models for the Treatment of TGF-ß-Induced Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is incurable, and its progression is difficult to control and thus can lead to pulmonary deterioration. Pan-histone deacetylase inhibitors such as SAHA have shown potential for modulating pulmonary fibrosis yet with off-target effects. Therefore, selective HDAC inhibitors would be beneficial for reducing side effects. Toward this goal, we designed and synthesized 24 novel HDAC6, HDAC8, or dual HDAC6/8 inhibitors and established a two-stage screening platform to rapidly screen for HDAC inhibitors that effectively mitigate TGF-ß-induced pulmonary fibrosis. The first stage consisted of a mouse NIH-3T3 fibroblast prescreen and yielded five hits. In the second stage, human pulmonary fibroblasts (HPFs) were used, and four out of the five hits were tested for caco-2 permeability and liver microsome stability to give two potential leads: J27644 (15) and 20. This novel two-stage screen platform will accelerate the discovery and reduce the cost of developing HDAC inhibitors to mitigate TGF-ß-induced pulmonary fibrosis.

Time-Dependent Solvent-Driven Solid-State Fluorescence-based Numeric Coding.

Controllable solid-state transformations can provide a basis for novel functional materials. Herein, we report a series of solid-state systems that can be readily transformed between amorphous, co-crystalline, and mixed crystalline states via grinding or exposure to solvent vapors. The present solid materials were constructed using an all-hydrocarbon macrocycle, cyclo[8](1,3-(4,6-dimethyl)benzene) (D4d-CDMB-8) (host), and neutral aggregation-caused quenching dyes (guests), including 9,10-dibromoanthracene (1), 1,8-naphtholactam (2), diisobutyl perylene-3,9-dicarboxylate (3), 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (4), 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (5), and 4-imino-3-(pyridin-2-yl)-4H-quinolizine-1-carbonitrile (6). Seven co-crystals and six amorphous materials were obtained via host-guest complexation. Most of these materials displayed turn-on fluorescence emission (up to 20-fold enhancement relative to the corresponding solid-state guests). The interconversion between amorphous, co-crystalline states, and crystalline mixtures could be induced by exposure to solvent vapors or by subjecting to grinding. The transformations could be monitored readily by means of single-crystal and powder X-ray diffraction analyses, as well as solid-state fluorescent emission spectroscopy. The externally induced structural interconversions resulted in time-dependent fluorescence changes. This allowed sets of privileged number array codes to be generated.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients.

Objective: To identify the gene subtypes related to immune cells of cholangiocarcinoma and construct an immune score model to predict the immunotherapy efficacy and prognosis for cholangiocarcinoma. Methods: Based on principal component analysis (PCA) algorithm, The Cancer Genome Atlas (TCGA)-cholangiocarcinoma, GSE107943 and E-MTAB-6389 datasets were combined as Joint data. Immune genes were downloaded from ImmPort. Univariate Cox survival analysis filtered prognostically associated immune genes, which would identify immune-related subtypes of cholangiocarcinoma. Least absolute shrinkage and selection operator (LASSO) further screened immune genes with prognosis values, and tumor immune score was calculated for patients with cholangiocarcinoma after the combination of the three datasets. Kaplan-Meier curve analysis determined the optimal cut-off value, which was applied for dividing cholangiocarcinoma patients into low and high immune score group. To explore the differences in tumor microenvironment and immunotherapy between immune cell-related subtypes and immune score groups of cholangiocarcinoma. Results: 34 prognostic immune genes and three immunocell-related subtypes with statistically significant prognosis (IC1, IC2 and IC3) were identified. Among them, IC1 and IC3 showed higher immune cell infiltration, and IC3 may be more suitable for immunotherapy and chemotherapy. 10 immune genes with prognostic significance were screened by LASSO regression analysis, and a tumor immune score model was constructed. Kaplan-Meier (KM) and receiver operating characteristic (ROC) analysis showed that RiskScore had excellent prognostic prediction ability. Immunohistochemical analysis showed that 6 gene (NLRX1, AKT1, CSRP1, LEP, MUC4 and SEMA4B) of 10 genes were abnormal expressions between cancer and paracancer tissue. Immune cells infiltration in high immune score group was generally increased, and it was more suitable for chemotherapy. In GSE112366-Crohn's disease dataset, 6 of 10 immune genes had expression differences between Crohn's disease and healthy control. The area under ROC obtained 0.671 based on 10-immune gene signature. Moreover, the model had a sound performance in Crohn's disease. Conclusion: The prediction of tumor immune score model in predicting immune microenvironment, immunotherapy and chemotherapy in patients with cholangiocarcinoma has shown its potential for indicating the effect of immunotherapy on patients with cholangiocarcinoma.

Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model / 中华医学杂志(英文版)

BACKGROUND@#Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.@*METHODS@#First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.@*RESULTS@#Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P  < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.@*CONCLUSIONS@#hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.

3D-printed vertebral body in anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy.@*METHODS@#This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data.@*RESULTS@#There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01).@*CONCLUSION@#3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.