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

Traumatic brain injury (TBI), a growing public health problem, is a leading cause of death and disability worldwide, although its prevention measures and clinical cares are substantially improved. Increasing evidence shows that TBI may increase the risk of mood disorders and neurodegenerative diseases, including Alzheimer's disease (AD). However, the complex relationship between TBI and AD remains elusive. Metabolic dysfunction has been the common pathology in both TBI and AD. On the one hand, TBI perturbs the glucose metabolism of the brain, and causes energy crisis and subsequent hyperglycolysis. On the other hand, glucose deprivation promotes amyloidogenesis via β-site APP cleaving enzyme-1 dependent mechanism, and triggers tau pathology and synaptic function. Recent findings suggest that TBI might facilitate Alzheimer's pathogenesis by altering metabolism, which provides clues to metabolic link between TBI and AD. In this review, we will explore how TBI-induced metabolic changes contribute to the development of AD.

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （n=120） and the control group （n=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（χ²=-3.26，P<0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （P<0.05，P<0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (P<0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

Objective:To explore the effect of ICX ? tablets on controlling the pollution of dental unit waterlines. Methods:From September 30, 2018 to February 23, 2019, convenience sampling was used to select dental chair unit (DCU) with the dental pulp professional brand of A-dec which was newly put into use in a stomatology hospital for numbering. Using the method of random number table, four DCUs were selected and included in this study, including two in experimental group and two incontrol group. In control group, distilled water was added into two DCUs in dependent water storage tanks. In experimental group, two DCUs independent water storage tanks were added with distilled water and ICX ? tablets. From the first day of clinical use, water samples were collected continuously for 7 days, and the ICX ? tablets group was continuously sampled for 12 weeks for bacterial culture, and the number and qualified rate of colonies were counted. Results:A total of 280 water samples were collected.The number of colonies at the water outlet of the new DCU that used distilled water added with ICX ? tablets as dental unit waterlines was lower than that of distilled water group from the first day, and the difference was statistically significant ( P=0.007) . The qualified rate of colony number at the water outlet of the new DCU that used distilled water added with ICX ? tablets as dental unit waterlines was higher than that of distilled water group from the second day, and the difference was also statistically significant ( P=0.007) . Conclusions:ICX ? tablets can effectively control the pollution of dental unit waterlines and can keep the number of colonies in dental unit waterlines at a low level for a long time, but it still needs to be combined with regular monitoring and enhanced disinfection.

BACKGROUND: Multifocal motor neuropathy (MMN), Lewis-Sumner syndrome (LSS), and many chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) are representative of acquired multifocal polyneuropathy and are characterized by conduction block (CB). This retrospective study aimed to investigate the demyelinating distribution and the selective vulnerability of MMN, LSS, and CIDP with CB (CIDP-CB) in nerves. METHODS: Fifteen LSS subjects (107 nerves), 24 MMN subjects (176 nerves), and 17 CIDP-CB subjects (110 nerves) were included. Their clinical information was recorded, blood and cerebrospinal fluid tests were conducted, and nerve conductions of the median, ulnar, radial, peroneal, and tibial nerves were evaluated. CB, temporal dispersion, distal motor latency (DML), and F-wave latency were recorded, and nerve conduction velocity, terminal latency index, and modified F-wave ratio were calculated. RESULTS: CB was more likely to occur around the elbow in CIDP-CB than in MMN (78.6% vs. 6.8%, P < 0.01) but less likely to occur between the wrist and the elbow than in LSS (10.7% vs. 39.3%, P < 0.05). Tibial nerve CB was most frequently observed in MMN (47.4%, P < 0.05). CIDP-CB was characterized by a prolonged DML in all nerves, and slow motor nerve velocity of the upper limb was significant when CB nerves were excluded (P < 0.05). CONCLUSIONS We report the different distributions of segmental and diffuse demyelination of the ulnar and tibial nerves in LSS, MMN, and CIDP-CB. These distinct distributions could help in differentiating among these conditions.
Humans ; Neural Conduction ; Peripheral Nerves ; Polyneuropathies ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ; Retrospective Studies

Objective At present no deep investigation has been done on the relationship between handgrip strength and appendicular lean mass (ALM) in patients with chronic obstructive pulmonary disease (COPD). The study aimed to explore the present situation of handgrip strength in patients with stable COPD and relationship between handgrip strength and ALM.Methods A total of 93 patients with stable COPD who hospitalized in our department from August 2016 to July 2017 were selected for the study. All the patients underwent handgrip strength test, body composition analysis, as well as the analysis of the relationship between handgrip strength and ALM.Results Multivariate linear regression analysis showed age(X1), education(X2), smoking(X3), course of disease(X4) and lower limb lean mass(X5) could be taken as predictive factors for the variation degree of handgrip strength (R2=50.5%), and multiple linear regression equation was Y=9.959-4.315X1+1.397X2+2.679X3-1.526X4+1.538X5. The variation degree decreased to 48.1% when the course of disease was removed from the model, 28.3% when the limb lean mass was removed, 26.5% when two variables were removed. The correlation coefficients of ALM, upper limb, lower limb and torso lean mass (\[22.32±3.25\]kg, \[6.48±1.05\]kg, \[15.83±2.26\]kg, \[22.27±3.22\]kg) with handgrip strength (\[32.27±7.27\]kgf) were respectively 0.484, 0.436, 0.496 and 0.496 (P＜0.01).Conclusion The handgrip strength in patients with stable COPD is closely associated with ALM, and the course of disease and the lower limb lean mass greatly affect the handgrip strength. Clinical workers should pay extra attention to the relationship in order to give timely clinical intervention.

To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.
Animals ; Biomarkers ; metabolism ; Doxorubicin ; toxicity ; Energy Metabolism ; Liver ; drug effects ; metabolism ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Metabolic Networks and Pathways ; Metabolomics ; Multivariate Analysis ; Oxidative Stress ; Rats

Objective To explore the relationship between genetic polymorphisms of CACNA1C that encoded the alc subunit of the L-type calcium channel and the efficacy of calcium channel blocker (CCB,Nifedipine extended release tablet/20 mg/d)in essential hypertension(EH)patients of Han Chinese in Wenzhou.Methods For the enrolled 103 EH patients,Multiplex Polymerase Chain Reaction(Muhi PCR)and matrix assisted laser desorption ionization time of flight MS(MLD1-TOF MS)were performed to detect their genotypes(rs216008,rs1051375,rs2299661,rs10848683,rs215976),blood pressure(BP)after CCB monotherapy was compared among patients with different genotypes.Results(1)Blood pressure was significantly reduced in all patients post CCB(P ＜ 0.05 vs.pre-CCB).(2)Diastolic blood pressure reduction was more significant in subjects with rs2299661 C/C genotype(wild genotype)than in subjects with rs2299661C/G and rs2299661G/G genotype(mutational genotype)[(12.46 ± 7.91)mm Hg (1 mm Hg=0.133 kPa)vs.(7.22±8.01)mm Hgand(5.93 ± 9.77)mm Hg,P＜0.05].(3)Systolic blood pressure reduction was more significant in subjects with rs216008 C/C genotype(wild genotype)than in subjects with rs216008 C/T genotype(mutational genotype)[(20.60 ± 12.35)mm Hg vs.(13.62 ±10.21)mm Hg,P ＜0.05].(4)Blood pressure reduction was similar between subjects with genotype of rs1051375,rs10848683 and rs215976.Conclusion EH patients with wild genotype of rs2299661 and rs216008 in CACNA1 C are more likely to be responders of CCB monotherapy.

This study was aimed to detect the expression level of cmtm 5 (CKLF-like MARVEL transmembrane domain containing member 5) gene in the bone marrow cells from patients with multiple myeloma (MM), and to investigate the correlation between the expression level of cmtm5 and various clinical characteristics. Real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to measure the expression levels of cmtm5 gene in the bone marrow cells collected from MM patients, and the MM cell lines, namely, RPMI8226 and CZ1 cells. The normal donor marrow specimens were used as the reference. The ratio of cmtm5 copy number to abl (Abelson murine leukemia viral oncogene homolog) gene copy number was used for indicating the expression level. The results showed that the expression level of cmtm5 gene was significantly down-regulated in bone marrow cells of 51 untreated or relapsed/refractory MM patient as compared to those of normal donor marrow cells (0.047+/-0.062 for the untreated or relapsed/refractory MM patients versus 0.255+/-0.333 for the normal, p<0.01). According to the International Staging System (ISS), the cmtm5 expression level in marrow cells of patients in ISS III stage was significantly lower than that in patients in ISS I stage (0.034+/-0.034 for the ISS III stage versus 0.103+/-0.109 for ISSI stage, p<0.01). Similarly, lower expression levels of cmtm5 gene were also found in two human MM cell lines (0.014+/-0.009 for RPMI8226 cells and 0.004+/-0.006 for CZ1 cells). After the MM patients were effectively treated, their expression levels of cmtm5 gene significantly increased (0.020+/-0.005 for the untreated patients versus 0.227+/-0.038 for the effectively treated patients, p<0.01). A significant negative correlation was observed between the expression level of cmtm5 gene and the number of bone marrow plasma cells (r=-0.307, p<0.05). However, the correlation was not found between the expression level of cmtm5 gene and the clinical characteristics, such as gender, age, hemoglobin level, or M-protein level, etc. It is concluded that the expression level of cmtm5 gene is abnormally lower in the bone marrow cells from the MM patients, and are associated with ISS stages. Furthermore, the expression level of cmtm5 gene is negatively correlated with the number of bone marrow abnormal plasma cells in MM patients, which suggests that the abnormally lower expression of cmtm5 may be involved in the pathogenesis of the MM patients.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; metabolism ; pathology ; Case-Control Studies ; Chemokines ; genetics ; metabolism ; Female ; Humans ; MARVEL Domain-Containing Proteins ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Staging ; Tumor Suppressor Proteins ; genetics ; metabolism ; Young Adult

OBJECTIVETo evaluate the effects of ALT, HBsAg and HBV DNA at the baseline, 4 and 12 weeks after lamivudine treatment on the long term (104 weeks) response in e antigen-negative chronic hepatitis B patients.

METHODS127 adult e antigen-negative chronic hepatitis B patients were enrolled in this study. All patients received treatment on LAM 100 mg/d for at least 104 weeks. The liver function, serum HBV markers and HBV viral load were regularly checked during the treatment. The effects of ALT, HBsAg and HBV DNA at the baseline, 4 and 12 weeks after lamivudine treatment on the response at 104 weeks were statistically analyzed.

RESULTSThe proportion of patients with serum HBV DNA less than 1000 copies / ml at 104 weeks after LAM treatment was 50.0% and 86.8% in patients with baseline ALT less than 5 ULN and ALT is more than or equal to 5 ULN, respectively (P less than 0.01). In patients with baseline HBsAg less than 2000 COI and HBsAg is more than or equal to 2000 COI, the proportion of patients with serum HBsAg less than 500 COI at 104 weeks after LAM treatment was 19.1% and 17.5%, respectively (P more than 0.05). the HBsAg serological conversion rates were respectively 2.1% and 2.5% , respectively (P more than 0.05), the proportion of patients with serum HBV DNA less than 1000 copies/ml was 61.7% and 67.5%, respectively (P more than 0.05). In patients with baseline HBV DNA less than 10(6) copies/ml and HBV DNA is more than or equal to 10(6) copies/ml, the proportion of patients with HBV DNA less than 1000 copies/ml were statistically different at 4 weeks and 12 weeks after treatment, however, the proportion of patients with HBV DNA less than 1000 copies/ml at 104 weeks after LAM treatment was 62.7% and 67.1%, respectively (P more than 0.05). In patients with HBV DNA less than 1000 copies/ml and HBV DNA is more than or equal to 1000 copies/ml at 4 weeks after treatment, the proportion of patients with HBV DNA less than 1000 copies/ml at 104 weeks after LAM treatment was 70.7% and 60.9%, respectively (P more than 0.05). In patients with HBV DNA less than 1000 copies/ml and HBV DNA is more than or equal to 1000 copies/ml at 12 weeks after treatment, the proportion of patients with HBV DNA less than 1000 copies/ml at 104 weeks after treatment was 78.8% and 38.1%, respectively (P less than 0.01).

CONCLUSIONe antigen negative chronic hepatitis B patients with baseline ALT is more than or equal to 5 ULN and HBV DNA less than 1000 copies/ml at 12 weeks after treatment have better virological response at 104 weeks after LAM treatment. The baseline HBsAg and HBV DNA load are associated with the virological response at 104 weeks after LAM treatment.

Administration, Oral ; Adult ; Aged ; Alanine Transaminase ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Viral ; blood ; Female ; Follow-Up Studies ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Viral Load ; Young Adult