[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

Objective To explore the application value of the deep learning image reconstruction algorithm(ClearInfinity,CI)combined with high tube voltage and low tube current low-dose computed tomography(LDCT)in lung screening.Methods A total of 216 patients underwent lung screening CT plain scan were selected.Patients were randomly divided into conventional-dose group(A group)and low-dose group(B group).Image reconstructed by using the iterative algorithm(ClearView+,CV)in group A,CV-60％,CI-30％,CI-60％,and CI-90％algorithms in group B.CT value,noise,image quality,and edge detail were conducted with both objective and subjective evaluations.Lung nodules were automatically detected by using computer-aided diagnosis software,and radiation doses were recorded.Results Images reconstructed with the CI showed significantly superior signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)than with the CV(P＜0.05).Additionally,there was a significant correlation in lung nodule detection performance between the CI and the CV(P＜0.05).The effective dose(ED)in group B was reduced by approximately 85.80％compared to group A(P＜0.01).Although the SNR and CNR were highest with CI-90％,the subjective image quality was lower than that of CI-60％.CI-60％and CI-90％showed same performance in lung nodule detection using artificial intelligence(AI)software.Conclusion The application of LDCT scanning protocol using the CI algorithm based on deep learning,combined with high tube voltage and low tube current is feasible for lung screening.It is recommended to use CI-60％in clinical diagnosis to improve the safety and diagnostic confidence of lung CT screening.

BACKGROUND:β-Defensin has the ability against influenza A virus and inhibits a series of inflammatory responses induced by influenza A virus infection within cells.There have been no reports on whether hemagglutinin 1 from influenza A virus can induce the secretion of mouse β-defensin and interferon-γ when acting in mouse tracheal epithelial cells.OBJECTIVE:To investigate the effect of recombinant hemagglutinin 1 on the production levels of mouse β-defensin and interferon-γ in mouse tracheal epithelial cells.METHODS:Primary mouse tracheal epithelial cell were divided into six groups:blank control group(Control),recombinant hemagglutinin 1 group(200 ng/mL),recombinant hemagglutinin 1+influenza A virus group,influenza A virus group(2×TCID50),recombinant hemagglutinin 1+inactivated influenza A virus group,and inactivated influenza A virus(I)group.After the mouse tracheal epithelial cells in each group were treated for 4,8,or 24 hours,hematoxylin-eosin staining was used for pathological observation.The mRNA levels of mouse β-defensin 2,3,and 4,and interferon-γ were detected by qRT-PCR.The protein levels of mouse β-defensin 2,3,and 4 were measured by enzyme-linked immunosorbent assay,and the protein expression of interferon-γ was detected by western blot.RESULTS AND CONCLUSION:(1)The recombinant hemagglutinin 1 acting alone or in combination with influenza A virus could cause different pathological changes in tracheal epithelial cells.Phenomena such as vacuolation,nuclear pyknosis and cell fusion could be observed in the cells.(2)Compared with the control group,recombinant hemagglutinin 1 alone or in combination with influenza A virus or inactivated influenza A virus significantly induced the production of mouse β-defensin 2,3,and 4(P<0.05)and interferon-γ in mouse tracheal epithelial cells(P<0.05).These results indicate that recombinant hemagglutinin 1 alone or in combination with influenza A virus can induce the production of mouse β-defensin 2,3,and 4 and interferon-γ in mouse tracheal epithelial cells.

[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.

Objective To investigate the value of synthetic MRI(syMRI)for evaluating structural changes of brain nuclei and white matter in patients with Parkinson disease(PD).Methods Forty-five PD patients(PD group)and 35 healthy controls(HC group)were prospectively enrolled.Head scanning with strategically acquired gradient echo sequence was performed,then syMRI was obtained with post-processing.The values of T1,proton density(PrD),R2* and magnetic sensitivity values(MSV)of nuclei and white matter were measured based on syMRI and compared between groups.The correlations of syMRI quantitative parameters of nuclei and white matter being significantly different between groups with neurological function scores of subject were analyzed,and a combined model was established using multivariate logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn,the efficacy of single syMRI quantitative parameter and combined model for diagnosing PD was evaluated.Results Compared with HC group,T1 and PrD values of bilateral caudate nuclei decreased,while MSV of bilateral substatia nigra and right red nucleus increased(all FDR correction P＜0.05),while T1 and PrD values of bilateral splenium of corpus callosum,PrD values of left posterior limbs of the internal capsule(PLIC),R2* values of bilateral PLIC and right genu of the corpus callosum decreased in PD group(all FDR correction P＜0.05).syMRI quantitative parameters of the above brain regions were correlated with scores of Montreal cognitive assessment and Hamilton anxiety scale(r=-0.390-0.416,all P＜0.01).The area under the curve of single syMRI quantitative parameter for diagnosing PD was 0.664-0.788,lower than that of combined model(0.905,Z=2.653-4.096,all P＜0.05).Conclusion SyMRI could be used to quantitatively evaluate structural changes of brain nuclei and white matter in PD patients.