Background Bipolar disorder is a severe mental disorder characterized by cycling between mania/hypomania and depression,yet its underlying pathophysiological mechanism remains unclear.Several prior studies have suggested a potential role for voltage-gated calcium channel subunit genes in the etiology of bipolar disorder,particularly in their influence on brain structure.Objective To investigate the differences in grey matter volume(GMV)for individuals with bipolar disorder compared to healthy controls,and to explore the potential influence of calcium channel voltage-dependent T-type α1 G subunit(CACNA1G)rs757415 polymorphism on GMV in bipolar disorder and clarify the specific brain regions associated with this genetic variation,thus offering a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder.Methods A cohort of 289 patients who met the Diagnostic and Statistical Manual of Mental Disorders,fourth edition(DSM-IV)criteria for bipolar disorder were selected for participation.These patients were either admitted to hospital or examined in outpatient clinic for bipolar disorder at the Mental Health Center of West China Hospital,Sichuan University between September 2013 and December 2022.Another 322 healthy individuals were concurrently recruited as a control group from Sichuan University and surrounding communities.All participants underwent brain imaging using a 3.0 T magnetic resonance scanner to acquire data on GMV.Additionally,the presence of the CACNA1G rs757415 polymorphism was validated using the imLDRTM technique.Spearman correlation analysis was utilized to investigate potential relationship between abnormal brain regions identified through GMV data and clinical characteristics of the patients.Then the genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed using the full factor method.Results The study successfully enrolled 173 patients with bipolar disorder and 207 healthy controls who completed all the necessary procedures.Analyses revealed decreased GMV for patients with bipolar disorder compared to healthy controls in the left cerebellar declive extending to cerebellar anterior/posterior lobe,fusiform gyrus,parahippocampal gyrus and inferior occipital gyrus(t=5.664,P<0.05);in the right cerebellar anterior/posterior lobe,fusiform gyrus,parahippocampal gyrus extending to lingual gyrus(t=4.583,P<0.05);in the bilateral anterior cingulate/paracingulate gyri,superior frontal gyrus and precuneus(t=7.543,P<0.05);in the left lingual gyrus and superior temporal gyrus(t=6.593,P<0.05);and in the right insula entending to central operculum(t=7.153,P<0.05).Correlation analysis indicated that the duration of bipolar disorder was positively correlated with cerebrospinal fluid volume(r=0.258,P=0.003),whereas negatively correlated with the GMV in the left cerebellar declive extending to cerebellar anterior/posterior lobe,inferior occipital gyrus and parahippocampal gyrus(r=-0.204,P=0.019),in the right cerebellar anterior lobe extending to right cerebellar posterior lobe,fusiform gyrus,parahippocampal gyrus and lingual gyrus(r=-0.238,P=0.006),in the bilateral superior frontal gyrus extending to anterior cingulate/paracingulate gyri and precuneus(r=-0.219,P=0.012),in the left lingual gyrus extending to superior temporal gyrus(r=-0.296,P=0.001),and in the right insula extending to central operculum(r=-0.257,P=0.003).A significant genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5(F=19.967,P<0.05).In the control group,individuals carrying the non-risk allele showed increased GMV in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5 compared to those carrying the risk allele.In contrast,within the patient group,risk allele carriers exhibited increased GMV in the same brain regions when compared to non-risk allele carriers.Moreover,the GMV in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5 of patients with bipolar disorder carrying risk alleles was increased compared to healthy controls.Conclusion CACNA1G rs757415 polymorphism may affect the GMV in the right parahippocampal gyrus,fusiform gyrus and cerebellum 4/5 of patients with bipolar disorder.

Objective:To assess the consistency of ultrasound and dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis(GA), reasons of the differences were further analyzed.Methods:The ultrasound and DECT images of 150 knee joints from 147 patients diagnosed with gout at the Gout Specialty Clinic of Qingdao University Affiliated Hospital from February 2022 to October 2023 were retrospectively analyzed. According to anatomy, the knee joint was anatomically segmented into five regions: intra-articular, anterior, posterior, medial, and lateral.Location of monosodium urate (MSU) deposition was meticulously recorded. The Kappa consistency test was employed to assess the consistency of the two examination results in different regions of the knee joint. The McNemar chi-square test was utilized to conduct a differential analysis between DECT and ultrasound results.Results:Double contour sign(DCS) (81.2%, 92/112) was the most common intra-articular ultrasound sign in knee joints with GA. In the extra-articular region, MSU was commonly deposited in and around the popliteal tendon (ultrasound: 51.6%, 66/128; DECT: 54.7%, 70/128). Corresponding MSU deposits on DECT were found in 9 of 92 joints with DCS and in 9 of 49 joints with aggregates detected on ultrasound.In the assessment of MSU deposits, ultrasound showed an overall higher positive rate than DECT (87.3% vs. 72.3%, P=0.001), with poor consistency between the two examinations (Kappa=0.153). In distinct anatomical regions, ultrasound and DECT showed high consistency in the medial (Kappa=0.697) and lateral (Kappa=0.718) sides and the difference was not statistically significant ( P>0.05). Intra-articular (Kappa=0.289) and anterior (Kappa=0.303) regions exhibited only fair consistency, with statistically significant diagnostic differences ( P<0.05). When exclusively assessing cases with tophus, ultrasound and DECT demonstrated high consistency in the medial and lateral aspects(Kappa=0.685, 0.748) without statistical difference ( P>0.05). In the anterior region, the consistency between the two examinations was moderate (Kappa=0.256), while in the intra-articular region, the consistency of the two methods was lower (Kappa=0.147), and the differences was statistically significant ( P<0.001). Conclusions:Both ultrasound and DECT exhibit good diagnostic capabilities for gouty knee arthritis.However, the consistency between the two techniques varies in different anatomical locations. Clinical assessment should be tailored based on the specific anatomical position. DECT has an advantage in evaluating intra-articular MSU deposits, while ultrasound is more sensitive to detect early and scattered MSU deposits.

Objective:To assess the discriminatory value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System (F-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and to compare its performance with other risk stratification systems(RSS).Methods:A retrospective analysis was conducted on 325 patients (327 thyroid nodules) diagnosed postoperatively as FTC or FTA at Affiliated Hospital of Qingdao University from January 2016 to December 2023. The cases were divided into FTC group (81 nodules) and FTA group (246 nodules). The nodules were classified based on F-TIRADS, the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS), the 2015 American Thyroid Association guidelines (ATA guidelines), and the 2017 European Thyroid Association Thyroid Imaging Reporting and Data System (EU-TIRADS) by two ultrasound physicians. Multivariate Logistic regression analysis was used to identify independent predictors associated with FTC. Diagnostic performance of the 4 RSS was compared using postoperative pathological results as the gold standard.Results:Multivariate Logistic regression analysis showed maximum diameter, solid composition, hypoechogenicity, unclear or angular margins, marginal or ring calcifications, trabecular structure, and central blood flow were independent predictors of FTC( OR=1.914, 3.427, 9.926, 9.163, 45.918, 3.191, 8.936, respectively; all P<0.05). Within each RSS, the actual malignancy rate increased with higher risk categories, aligning closely with the recommended malignancy rates (except for ATA guidelines). The optimal cut-off values for distinguishing FTC from FTA were FTC risk 50%-90% in F-TIRADS, C-TIRADS 4B, moderately suspicious nodules in ATA guidelines, and EU-TIRADS 4, with areas under the curve of 0.916, 0.808, 0.827, and 0.836, respectively. F-TIRADS demonstrated the best overall performance (sensitivity: 82.72%, specificity: 82.93%), with significant differences compared with C-TIRADS, ATA guidelines, and EU-TIRADS (all P<0.05). Conclusions:F-TIRADS is highly effective in distinguishing FTA from FTC, outperforming C-TIRADS, ATA Guidelines, and EU-TIRADS. Clinicians should pay close attention to solid hypoechoic nodules with unclear or angular margins, marginal or ring calcifications, central blood flow, or a trabecular structure.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

A 10-day-old male infant presented with skin erythema and blisters for 6 days. Skin examination showed scattered or confluent erythema all over the body, tense blisters of varying sizes on the normal skin or an erythematous base, and some blisters were ulcerated and erosive; bloody bullae and erythematous erosive patches could be seen on the oral mucosa. Histopathological examination revealed subepidermal blisters, and there were some neutrophils and a few eosinophils in the blisters. Direct immunofluorescence assay showed homogeneous linear IgA and granular C3 deposits along the basement membrane zone, without IgG deposits. The diagnosis of neonatal linear IgA bullous dermatosis was confirmed. After comprehensive treatments including nutritional support and anti-infection treatment, skin erythema and blisters subsided, and the mucosal damage was attenuated. The telephone follow-up 16 months after discharge showed that the infant was in good general condition with normal growth and development, and the oral mucosal lesions had subsided and healed, without new skin lesions.

Objective To investigate the seasonal Aedes population fluctuation and the resistance of Aedes populations to common insecticides in Jiangsu Province in 2020, so as to provide insights into vector-borne infectious diseases control.. Methods One village was randomly sampled from each of Xinbei District of Changzhou City and Zhangjiagang County of Suzhou City in southern Jiangsu Province, Hai’an County of Nantong City and Yandu District of Yancheng City in Central Jiangsu Province, and Suining County of Xuzhou City and Sihong County of Suqian City in northern Jiangsu Province during the period between May and October, 2020. A small ponding container was sampled, and larval Aedes mosquitoes were collected using straws once each in early and late stages of each month. All larvae were bred in laboratory to adults for population identification. In addition, larval breeding were observed in all small ponding containers in and out of 30 households that were randomly sampled from six surveillance sites, and the larval mosquito density was estimated using Breteau index. Larval A. albopictus mosquitoes were sampled around Cuiyuan New Village in Jintan District of Changzhou City, and bred in laboratory to the first offspring generation, and the susceptibility of adult female mosquitoes to deltamethrin, lambda-cyhalothrin, malathion, and propoxur was tested using the filter-paper bioassay recommended by WHO. Results A total of 1 165 larval Aedes mosquitoes were captured from small ponding containers in six surveillance sites of Jiangsu Province in 2020, and all were identified as A. albopictus following eclosion. The largest number of Aedes larvae captured was found in July. A total of 1 152 households were investigated in six surveillance sites, and the mean Breteau indexes were 9.58, 13.20, 13.71, 13.20, 12.18 and 5.58 from May to October, respectively, while a high Aedes transmission risk was seen in Xinbei District of Changzhou City, with a higher Breteau index than in Suining (H = 23.667, P_adjusted = 0.001) and Sihong (H = 22.500, P_adjusted = 0.003) counties. The field-captured A. albopictus from Cuiyuan New Village in Jintan District of Changzhou City remained sensitive to malathion, but was resistant to propoxur, and developed high-level resistance to deltamethrin and lambda-cyhalothrin. Conclusions A. albopictus was present in southern, central and northern Jiangsu Province in 2020, and the larval density peaked in July. A. albopictus captured from Cuiyuan New Village in Jintan District of Changzhou City has developed high-level resistance to pyrethroid pesticides.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To summarize the genetic characteristics of a case of spinal muscular atrophy type 1c.Methods:The case data of a child with spinal muscular atrophy type 1c was retrospectively analyzed, and the genetic analysis and literature review were carried out.Results:The patient, male, started at the age of 2 months, and showed gross motor development backwardness and low muscular tension. Multiplex connection probe amplification technique showed that the child had homozygous deletion mutation in exon 7-8 of SMN1 gene, and there was duplicate mutation in exon 7-8 of SMN2 gene. The number of copies of exon 7/8 was 3/3. His father was a heterozygous deletion carrier of SMN1 gene, and there was homozygous mutation in exon 8 of SMN2 gene. The number of copies of exon 7/8 was 2/3. His mother did not find abnormal exons of SMN1 gene, and the number of copies of exon 7/8 of SMN2 gene was 1/1.Conclusion:Spinal muscular atrophy lacks specific manifestations in the early stage, and the diagnosis mainly depends on genetic testing. Clinicians need to be vigilant, strengthen the early understanding of the disease, and improve the prognosis.

Objective:To establish a solvent desorption gas chromatographymethod for the determination of phenyl glycidyl ether (PGE) .Methods:From October to December 2020, PGE in the air of workplace was collected with carbon tube and desorbed by 25% acetone-carbon disulfide. The target toxicant was separated with the gas chromatography (GC) column and analyzed with flame ionization detector (FID), and quantified by peak area.Results:The linear range of PGE in the air of workplace was 10.0-1109.0 μg/ml, the linear equation was y=1.156 x-4.328, with a correlation coefficient of 0.9997. The limit of detection was 3.0 μg/ml. The lower limit of quantification was 10.0 μg/ml. The intar-batch and inter-batch precisionswere 4.9%-6.4% and 6.2%-6.9%, respectively. The recovery rate was ranged from 97.2%-98.8%, the average collection efficiency was 100%, and the average extraction efficiency was 90.1%. The samples could be stored at 4 ℃ for 7 d. Conclusion:This method has high precision and good accuracy, and it is applicable for the determination of PGE in workplace air.