OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

This study utilized ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) to rapidly analyze and identify the chemical constituents in five processed products of Strychni Semen(raw, sand-roasted, fried, urine-soaked, and vinegar-processed products). Using PeakView software to extract compound information, 50 chemical components were identified based on retention time, accurate molecular ion peaks, secondary mass spectrometry data, and comparison with reference standards and relevant literature. Specifically, 41 components were identified in raw Strychni Semen, 48 in sand-roasted, 43 in fried, 41 in urine-soaked, and 40 in vinegar-processed products. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to identify differential components among the processed products, with variable importance in projection(VIP) values>1 and a t-test with P<0.05 as criteria. PCA revealed significant differences among the five processed products, demonstrating good clustering and separation. OPLS-DA identified 13 differential components, including brucine, strychnine, loganic acid, and chlorogenic acid. The results indicated that S. nux-vomica primarily contained alkaloids, organic acids, and glycosides, with significant compositional differences among the various processed products. Notably, the content of key components such as brucine and strychnine decreased after processing, with the most significant reduction observed in vinegar-processed Strychni Semen. In conclusion, this study provides a comprehensive comparison of the effects of different processing methods on the chemical composition of Strychni Semen, exploring the differences in the material basis of the processed products and offering data to support the scientific rationale behind the processing of Strychni Semen.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/analysis* ; Mass Spectrometry/methods* ; Strychnos/chemistry* ; Principal Component Analysis

Objective To study the expression of adhesion molecules CD44 and ICAM-1 in BALB/c mice infected with Mycoplasma pneumoniae (MP) and elucidate the relationship between MP and infection.Methods BALB/c mouse MP model was established by MP nasal instillation,and the pathological changes of lung in MP mice were observed.The expression levels of adhesion molecules CD44 and ICAM-1 in serum and bronchoalveolar lavage fluid of mice infected with 5,8,15,20 and 30d MP were determined by ELISA.Results Compared with the model group,MP infected BALB/c mice after lung inflammation was significantly up-regulated MP,the expression in BALB/c mice infected with the serum and bronchoalveolar layage fluid in CD44 and adhesion molecule ICAM 1 (t5 d serum CD44 =53.64 ng/L,t5 d BALF CD44 =144.3 ng/L;t5 d serum ICAM-1 =73.72 ng/L,t5 d BALF ICAM-1 =165.06 ng/L,all P＜ 0.000;t8 d serum CD44 =40.86 ng/L,t8 d BALF CD44 =21.31 ng/L;t8 d serum ICAM-1 =30.57 ng/L,t8 d BALF ICAM-1 =19.61 ng/L,all P＜0.000).The Mycoplasma pneumoniae infection increased the expression levels of adhesion molecules CD44 and ICAM-1 in mice.Conclusion After MP mice were cured,the expression of CD44 and ICAM-1 was down regulated,and the up regulation of CD44 and ICAM-1 expression might be related to the severity of MP pneumonia.

Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P < 0.05); however, the levels of plasma adrenaline in two groups had no statistical differences (P > 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). Conclusions As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.

Objective: To explore the relationship between ABO blood group and acute non-ST-segment elevation myocardial infarction (NSTEMI) occurrence. Methods: Our research included 2 groups: NSTEMI group, 1039 relevant patients treated in Anzhen hospital from 2013-01 to 2014-12 were retrospectively enrolled; Control group, 1039 subjects with normal coronary artery which was confirmed by coronary angiography. The Baseline condition including age, previous disease history and ABO blood group was studied. Logistic regression model was used to conduct single and multivariate analysis. Results: In NSTEMI group and Control group, blood type A was 287/1039 (27.6％) vs 259 (24.9％), type B was 345 (33.3％) vs 356 (34.3％), type AB was 102 (9.8％) vs 114 (11.0％) and type O was 305 (29.4％) vs 310 (29.8％), ABO blood group distribution for A and non-A, B and non-B, AB and non-AB blood group, O and non-O had no statistic meaning between 2 groups, P>0.05. Logistic regression analysis indicated that with adjusted risk factors of MI such as age, gender, hypertension, diabetes, hyperlipemia, cerebrovascular disease and smoking, the patients with blood types A, B and AB had the similar risk for NSTEMI occurrence than type O patients; there was no relationship between ABO blood group and NSTEMI occurrence. Conclusion: ABO blood group had no relationship to NSTEMI occurrence.

To establish a method for determining the contents of six alkaloids (jatrorrhizine hydrochloride, columbamine hydrochloride, epiberberine hydrochloride, coptisine hydrochloride, palmatine hydrochloride, berberine hydrochloride) in six types of Coptidis Rhizoma pieces (crude pieces, ginger juice stir-fried pieces, vinegar stir-fried pieces, wine steamed pieces, wine stir-fried pieces, evodiae juice stir-fried pieces) by RP-HPLC, and explore the relationship with the curative effect of traditional Chinese medicine (TCM) and pharmacodynamics results. The chromatographic column was Welch XtimateTM C₁₈ (4.6 mm×250 mm, 5 μm), with 0.1% triethylamine solution (adjust pH at 10 with ammonium bicarbonate and ammonia) as mobile phase A and acetonitrile as mobile phase B for gradient elution (0-15 min, 10%-25%B; 15-25 min, 25%-30%B; 25-40 min, 30%-45%B) at a rate of 1.0 mL•min⁻¹. The column temperature was set at 30 ℃, and the wavelength was set at 270 nm. The six alkaloids showed a good linear relationship within the range of 0.85-16.96 mg•L⁻¹ (r=0.999 7), 1.25-24.96 mg•L⁻¹ (r=0.999 9), 2.05-40.96 mg•L⁻¹ (r=0.999 9), 3.65-72.96 mg•L⁻¹ (r=0.999 9), 2.88-57.60 mg•L⁻¹ (r=0.999 8), and 13.25-264.96 mg•L⁻¹ (r=0.999 6) respectively. The average recoveries (n=9) of the six alkaloids were 102.4% (RSD 1.2%), 101.8% (RSD 1.3%), 100.3% (RSD 1.8%), 100.7%(RSD 1.8%), 101.2% (RSD 1.5%) and 97.90% (RSD 2.0%) respectively, and their average contents were 3.55, 4.49, 9.12, 19.17, 15.69, 62.56 mg•g⁻¹, respectively. This determination method was accurate and repeatable, which could be used for the content determination in six types of Coptidis Rhizoma pieces. Data analysis on contents determination and preliminary pharmacodynamics results was conducted by using principal component analysis (PCA) and hierarchical clustering analysis (HCA). The analysis results showed that three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces) had significant differences with crude pieces, and the wine steamed Coptidis Rhizoma pieces showed most difference with crude pieces especially, mainly related to triglyceride (TG) and fasting blood glucose levels (FBG) in serum. In addition, columbamine hydrochloride was most affected among the six alkaloids. Those three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces), had more advantages for "anti-diabetes" in TCM clinical application, especially in the treatment of diabetic hyperlipidemia.

Objective To identify the risk factors for reported sudden rise of measles incidence in November,2011,in some areas of Hubei province.Methods We analyzed all measles patients reported in the measles surveillance system from November 2011 to February 2012 in two prefectures with highest attack rates and their vaccination history by reviewing vaccination records.We interviewed patients' parents by telephone to obtain the history of visiting health care within 7 to 21 days before onset.We also used case-crossover study to estimate the relative risk (RR) of hospital acquired infection and to compare the exposure to health care between 7-21 days before onset to 37-51 days before onset among measles patients.Results Totally 140 patients were reported in the two prefectures.Reported measles incidence rates among the population aged ＜8 m (69/100 000) and 8 m to 17 m (72/100 000) were higher than other age groups (rang from 0 to 5.8 per 100 000).Among the population aged 8 m to 17 m,estimated vaccination coverage was lower than 75％,and it was lower than 90％ among those aged 18 m to 3 yrs.During 7-21 days before onset,58％(29/50) of the patients had an exposure to health care settings,compared to 14％ (7/50) of patients during 37 to 51 days before onset (MH RR=5.4,95％ confidence interval=2.1-14.0).Conclusion Under the condition of measles vaccination coverage lower than 95％,iatrogenic infection was a risk factor for measles in Hubei.

OBJECTIVETo evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features.

METHODSFrom year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively.

CONCLUSIONThe study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; Chromium ; blood ; urine ; Female ; Humans ; Male ; Middle Aged ; Population Surveillance ; Young Adult