SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective:To introduce the construction of Henan Cerebral Palsy Register and Rehabilitation Management System (HCPRRMS) and to explore the construction project of regional register and surveillance of cerebral palsy. Methods:The construction process, registration content and preliminary results of HCPRRMS were systematically introduced. Results:HCPRRMS was independent developed in 2014. Since March, 2015, the system has been used to register information of patients with cerebral palsy in the Third Affiliated Hospital of Zhengzhou University. Until September, 2019, a total of 23 child rehabilitation institutions had used the registration management system. There were 1357 patients with cerebral palsy registered in this system, in which 936 cases (68.98%) were male, 501 cases (36.92%) were with gestational weeks < 37, 443 cases (32.65%) were with birth weight < 2500 g, and 430 cases (31.69%) were born with hypoxic-ischemic encephalopathy. Among them, the spastic cerebral palsy patients (1117 cases, 86.74%) accounted for the highest proportion. There was significant difference among types of cerebral palsy and the classification of GMFCS. A total of 1117 patients with cerebral palsy showed MRI-identified brain abnormalities, in which, periventricular leukomalacia accounted for the most (480 cases). For the complications, epilepsy accounted for 14.44% (196 cases), vision impairment accounted for 8.03% (109 cases), hearing impairment accounted for 11.64% (158 cases). Among 769 cases aged more than two years, language-speech dysfunction accounted for 52.66% (424 cases); and among 216 cases aged more than four years, mental retardation accounted for 37.96% (82 cases). Conclusion:HCPRRMS could help to understand the risk factors, clinical characteristics, and complications of cerebral palsy.

There are many kinds of processed products of Aconiti Lateralis Radix Praeparata (ALRP), but their differences in toxicity and efficacy have not been identified. The minimum premature ventricular contraction (PVC) method was used to evaluate the biological toxicity of eight processed products. The results showed that the minimal toxic dose (MTD) of an ethanol extract of Shengfupian (SFP) was 0.16 g·kg^-1, which was much lower than that of Heishunpian (HSP), Baifupian (BFP), Baofupian (BAP), Paofuzi (PFZ) or Zhengfupian (ZFP), with MTDs ranging from 2.64 to 5.75 g·kg^-1. No cardiotoxicity was detected with Chaofupian (CFP) and Paotianxiong (PTX). A novel +dp/dt_max assay for acute heart failure in rats was developed to evaluate the cardiac activity. It was found that all eight processed products had cardiac effects, with Shengfupian showing the strongest cardiotonic effect and the ability to restore damaged cardiac function to normal within 15 minutes of injection. Heishunpian, Baifupian and the three other products displayed moderate activity, while Paofuzi and Paotianxiong were the weakest. An LC-MS/MS method was utilized to determine the content of 13 alkaloids in water extracts. The results demonstrated that hypertoxic aconitine, mesaconitine, and hypaconitine could not be detected, higenamine was only present in Shengfupian, and salsolinol was about 4-56 times higher in Shengfupian than in other products. A correlation analysis showed that salsolinol had the best correlation with the cardiotonic index, with a correlation coefficient as high as 0.817, while the three monoester alkaloids failed to correlate with the cardiotonic effect. Higenamine and salsolinol were cardiotonic, while the 11 other components had no cardiotonic activity. This study establishes methods for precise evaluation of cardiotoxicity and cardiac activity, reveals the toxicity and efficacy of common processed products, and identifies the key quality markers for cardiac activity, providing scientific support for the quality evaluation and clinical application of processed products of aconite.

Xiaojin pills, the first choice for clinical treatment of breast hyperplasia, were selected to explore the suitability of a bioactivity assay with chemical fingerprinting for the development of an overall quality evaluation assay. The liposoluble and water-soluble fraction fingerprints of Xiaojin pills were established. The ability to inhibit platelet aggregation and the rate of inhibition of cyclooxygenase-2 (COX-2) for 16 batches of Xiaojin pills from several manufacturers was analyzed; the chemical fingerprints of these samples were correlated with the bioactivity and chemical analysis. The animal protocol was approved by the Committee on the Ethics of Animal Experiments of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Approval, ID: 2018BL-002. Results showed that the antiplatelet aggregation activity of 16 batches was 0.712-1.278 U∙mg^-1, with a relative standard deviation (RSD) of 15.4%. COX-2 inhibition was 52.07%-68.95% and the RSD was 8.91%. The results showed that there was little difference in the biological effects of these samples. However, the chemical fingerprint consistency of these 16 batches of Xiaojin pills was poor, and the similarity of nearly half of the samples was less than 0.9. The total peak area of Xiaojin pills was 32.74%-165.37% across samples, showing very poor chemical consistency. In order to explore the reasons for the poor chemical consistency despite good consistency in the biological assays, the fingerprint chromatogram was analyzed by multivariate statistical analysis. The main chromatographic peaks were identified. The results showed that the similarity of Xiaojin pills was mainly determined by the prominent chromatographic peaks 17, 18, 20, 23 and 27 in the liposoluble fingerprints, which were identified from Liquidambaris resina and Angelica sinensis Radix. However, Liquidambaris resina and Angelicae sinensis Radix had almost no anti-platelet aggregation activity or COX-2 inhibitory effect at the normal prescription ratio. As a result, the ability to utilize chemical fingerprints to evaluate the quality consistency of Xiaojin pills is limited. The selection of biological evaluation methods that reflect clinical efficacy could make up for the shortcomings of chemical evaluation methods for quality assessment, and provide new ideas and methods for the overall quality evaluation of complex Chinese patent medicines.

ObjectiveTo investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV).

METHODSThis study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA.

RESULTSCompared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (［255.18 ± 69.97］ vs ［141.78 ± 59.82］ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (［255.18 ± 69.97］ vs ［412.44 ± 259.42］ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = －0.224, P < 0.01).

CONCLUSIONSThe level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.

Adolescent ; Antibodies ; blood ; Biomarkers ; blood ; Child ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; blood ; Luteinizing Hormone ; blood ; Male ; Spermatozoa ; immunology ; Testosterone ; blood ; Varicocele ; blood

BACKGROUND AND PURPOSE: Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. METHODS: We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. RESULTS: Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P < 0.001), severer luminal stenosis (25%±21% vs. 12%±9%, P=0.002), higher rate of concentric lesions (79% vs. 36%, P=0.002), and denser intraplaque calcification (44% vs. 0%, P=0.003). Histologically, intracranial VA with VV had a larger diameter (3.40±0.79 mm vs. 2.34±0.58 mm, P < 0.001), thicker arterial wall (0.31±0.13 mm vs. 0.23±0.06 mm, P=0.002), and a larger intima-media (0.19±0.09 mm vs. 0.13± 0.04 mm, P=0.003) than VA without VV. CONCLUSIONS: Our study demonstrated the distribution of adventitial VV within brain vasculature and association between vertebral VV and progressive atherosclerotic lesions with a heavier plaque load and denser intraplaque calcification.
Arteries ; Atherosclerosis ; Autopsy ; Basilar Artery ; Brain ; Cerebral Arteries ; Constriction, Pathologic ; Humans ; Intracranial Arteriosclerosis* ; Middle Cerebral Artery ; Phenobarbital ; Vasa Vasorum* ; Vertebral Artery

On basis of the idiosyncratic lipopolysaccharide(LPS)-mediated hepatotoxicity model, liver injury induced by Zhuangguguanjie wan(ZGW)was evaluated, and the mechanism was explored. Idiosyncratic hepatotoxicity model was established in rats by injecting LPS at a dosage of 2.8 mg·kg^-1. Rats were randomly divided into the normal control group, LPS group, ZGW group and LPS+ZGW group. Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were analyzed in serum; pathological changes(HE staining)and the content of cytokines of liver were tested; and immune cell subpopulation ration were determined in blood and liver. Compared with the control group, the ZGW group and LPS group had no significant changes in ALT, AST and liver pathology(P> 0.05); while the ZGW+LPS group exhibited an elevation in ALT and AST(P< 0.05). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in the group. Several cytokines in the liver were increased in LPS group and ZGW+LPS group(P< 0.05 or P< 0.01), and the level in ZGW+LPS group was higher than that of LPS group. Compared with the control group, the ratio of CD3⁺ T cell/lymphocyte of blood in LPS group was significantly decreased(P< 0.01); while the percentage of CD3⁺ T cells in the liver were significantly increased(P< 0.05). The contents of immune cells of blood had no significant changes between LPS group and ZGW+LPS group(P> 0.05). CD3⁺ T cell in the liver of ZGW+LPS group was significantly increased over the LPS group(P< 0.05). Aggregation or activity of CD3⁺ T cell was increased by ZGW combined with LPS. These results suggest that ZGW could promote T lymphocyte recruitment to liver under the immune activation state leading to inflammatory response, which may contribute to idiosyncratic liver injury.

According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention.

BACKGROUNDPulmonary embolism (PE) is often mistaken as acute coronary syndromes (ACS) because of the considerable overlap in their clinical features. We evaluated the factors causing misdiagnosis of PE as ACS and factors that differentiate PE from ACS to improve the diagnosis efficacy of PE.

METHODSThe medical records of 22 consecutive PE patients, between 2001 and 2010, who were initially suspected of ACS were retrieved. ACS was ruled out by coronary artery angiography before a definite diagnosis of PE was given. Twenty-two contemporary cases of ACS matched by age and sex were recruited as controls. Clinical manifestations, electrocardiograms (ECG), and biomarkers of these patients were reviewed retrospectively. The factors causing misdiagnosis of PE as ACS and factors differentiating PE from ACS were evaluated.

RESULTSWe found two leading causes of misdiagnosis of PE as ACS. One is that PE can resemble ACS in several clinical aspects (symptoms and signs, ECG findings, plasma cardiac troponin I, and D-dimer). The other is the insufficient recognition of PE by clinicians. Risk factors for venous thromboembolism (VTE), especially deep venous thrombosis (DVT), together with signs of PE, such as unexplained dyspnea or hypoxemia, and right ventricular pressure overload on ECGs are valuable in differentiating the two diseases.

CONCLUSIONSDifferentiation between PE and ACS is sometimes challenging. Adequate awareness of the risk factors for VTE and the signs of PE are crucial in the diagnosis of PE.

Acute Coronary Syndrome ; diagnostic imaging ; Adult ; Aged ; Coronary Angiography ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Embolism ; diagnostic imaging ; Retrospective Studies

Adult ; Chondroblastoma ; pathology ; Chondroma ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Ovarian Neoplasms ; pathology ; surgery ; Ovary ; pathology ; Teratoma ; pathology