Objective To investigate the utility of dual-energy CT combined with musculoskeletal ultraso-nography in differentiating between calcium pyrophosphate deposition disease and gouty arthritis.Methods A retro-spective analysis was conducted on the medical records of 102 patients diagnosed with gouty arthritis and 102 patients diagnosed with calcium pyrophosphate deposition disease.These patients were categorized into the Gout group and Calcium Deposition group,respectively,based on their respective diagnoses.All patients underwent dual-energy CT and musculoskeletal ultrasonography examinations,while joint fluid aspiration results or intra-articular crystal material served as the gold standard for diagnosis.The diagnostic efficacy of dual-energy CT and musculoskeletal ultrasonography in discriminating between calcium pyrophosphate deposition disease and gouty arthritis was evalu-ated.Results In the gout group,the proportion of male patients and serum uric acid levels were significantly higher compared to those in the calcium deposition group(P<0.05).The prevalence rates of knee joint,first metatarsopha-langeal joint,and ankle joint involvement were higher in the gout group,while knee joint,wrist joint,and shoulder joint involvement rates were higher in the calcium deposition group.The proportions of irregular bone cortex,carti-lage injury,and degenerative meniscus changes were lower in the gout group compared to the calcium deposition group(P<0.05).The proportions of double contour sign,tophus formation,hyperechoic band within ligaments or tendons,and bone erosion were higher in the gout group compared to the calcium deposition group(P<0.05),whereas cartilage calcification was lower in the gout group(P<0.05).The sensitivities for diagnosing calcium pyrophosphate deposition disease and gouty arthritis using dual-energy CT scan alone,musculoskeletal ultrasound alone,and their combined use were 86.27%,83.33%,and 94.12%respectively.The specificities for diagnosing these conditions using dual-energy CT scan alone,musculoskeletal ultrasound alone,and their combined use were 89.22%,88.24%,and 86.27%respectively.The positive predictive values were 88.89%,87.63%,and 87.27%,respectively.The negative predictive values were 86.67%,84.11%,and 93.63%,respectively.The accuracies were 87.75%,85.78%,and 90.20%respectively.The agreement Kappa values were 0.755,0.716,and 0.804 respectively.Conclusions The integration of dual-energy CT and musculoskeletal ultrasonography exhibits promising diagnostic efficacy in discriminating between calcium pyrophosphate deposition disease and gouty arthritis.This combined approach serves as a valuable adjunctive tool for the diagnosis of both conditions.

Vascular cognitive impairment(VCI)includes a range of illnesses from mild cognitive impairment to dementia,attributable to cerebrovascular factors.Although appropriate animal models are needed to allow clinicopathological research and drug development,there are currently no animal models that can perfectly simulate the pathogenesis of VCI.At present,carotid artery and vertebral artery stenosis or occlusion are the main method for VCI modeling;however,increasing numbers of non-surgical method have recently emerged,providing new ideas and prospects for the study of this disease.In this paper,we consider the construction method,model mechanisms,and model characteristics of non-surgical animal models of VCI,to provide a reference to help researchers choose the most suitable animal model.

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D₂ receptor (D₂R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D₂R⁺ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D₂R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D₂-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D₂R⁺ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D₂R⁺ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D₂R⁺ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D₂R⁺ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

BackgroundThe obsessive-compulsive disorder （OCD） features complexity in etiological factors and high heterogeneity in clinical manifestations. OCD patients with different ages of onset vary in clinical symptoms and etiology. However， current studies on inpatients with early- and late-onset OCD are limited. ObjectiveTo explore the differences in clinical characteristics between early- and late-onset OCD inpatients as well as the factors affecting the onset age of OCD， so as to provide references for early screening and treatment of OCD patients. MethodsThis study was based on collected medical records of 540 patients with OCD who received inpatient treatments at the Affiliated Brain Hospital of Nanjing Medical University between March 2012 and March 2023. Patients with onset age above 18 were placed into early-onset group （n=310） and the others into late-onset group （n=230）. Then differences in demographic data and clinical symptoms between two groups of patients were compared. Binary logistic regression was used to analyze the factors that affect the onset age of OCD. ResultsObserving the demographic data， there were significant differences between the two groups in the results in gender， marital status， family history of mental illness， ratio of comorbidities with other mental illnesses， occupational composition， education level and types of obsessive-compulsive symptoms （χ²=22.302、170.556， 9.224， 13.624， 242.277， 59.791， 7.231， P<0.05 or 0.01）. Also， the results in ages of onset and hospitalization between two groups were significantly different （Z=-19.915， 16.831， P<0.01）. In terms of clinical symptoms， the early onset group had a higher proportion of symptoms including obsessive thinking （χ²=11.998， P<0.05）， ordering （χ²=7.731， P<0.05） and rituals （χ²=7.714， P<0.05）， while the proportion of obsessive checking （χ²=8.204， P<0.05） and washing （χ²=7.506， P<0.05） symptoms were relatively low. In terms of risk factors， there were several independent risk factors that influence the onset age of OCD inpatients， including comorbid neurodevelopmental disorder， comorbid affective disorder， family history of schizophrenia and family history of affective disorder （OR=19.587， 1.830， 3.065， 4.431， P<0.05）. Among them， comorbid neurodevelopmental disorder was the core influencing factor， and female gender was a protective factor for early-onset patients （OR=0.417， P<0.01）. ConclusionThere are differences in demographic data and clinical symptom characteristics between early- and late-onset OCD inpatients， and comorbid neurodevelopmental disorder plays as a core risk factor affecting the onset age of OCD inpatients. ［Funded by Jiangsu Province Key Research and Development Plan for Social Development Special Project（number， BE2021616） ； Jiangsu Province Social Development General Project （number， BE2022678）； Key Project of Nanjing Medical Science and Technology Development Fund （number， ZKX20029）］

Objective:To investigate the effect of irradiation on the expression of miR-150-5p and miR-23a-3p in human peripheral blood serum by collecting peripheral blood of tumor patients before and after radiotherapy, so as to provide scientific basis for finding radiation biomarkers.Methods:A total of 63 tumor patients treated with radiotherapy from October 2021 to March 2022 were enrolled in this study. The relative expression levels of miR-150-5p and miR-23a-3p in peripheral blood serum in these patients were detected using the real-time fluorescence quantitative PCR (qPCR) before and after radiotherapy. The differential changes in the expression levels of the two miRNAs in the peripheral blood serum of the patients before and after radiotherapy were compared, and their relationships with factors such as cancer types were analyzed.Results:The relative expression levels of miR-150-5p and miR-23a-3p in peripheral blood serum of the patients after radiotherapy were significantly lower than those before radiotherapy ( t = 4.97, Z = -2.77, P < 0.05). Among different cancer types, the relative expression level of miR-150-5p in the patients with breast cancer, esophageal cancer, or other digestive tract cancer decreased after radiotherapy ( t = 3.47, 2.47, 2.87, P < 0.05), and the relative expression level of miR-23a-3p in the patients with digestive tract cancer decreased after radiotherapy ( Z = -1.99, P < 0.05). The changes in the expression level of miR-150-5p before and after radiotherapy were not affected by gender, age, chemotherapy, and cancer type ( P > 0.05). By contrast, the changes in the expression level of miR-23a-3p before and after radiotherapy were significantly affected by gender, age, and chemotherapy ( t=2.04, -3.34, -2.29, P<0.05). Conclusions:The expression of miR-150-5p in the serum of tumor patients may be affected by radiotherapy, which has the potential to be used as a biological indicator of radiation.

Unilateral primary aldosteronism (UPA) is a common form of PA that is surgically curable by adrenalectomy of the overactive gland. Pathological evaluation of resected adrenals is crucial in the diagnosis of UPA, and its subsequent treatment and follow-up as well. Histomorphological evaluation is the basis for the pathological diagnosis of UPA, and the wide use of aldosterone synthase immunohistochemical staining in recent years has greatly improved the pathological diagnosis of UPA. However, there is a lack of standardized nomenclature and diagnostic criteria. Therefore, consensus on the histopathologic diagnosis of UPA were developed by an international group of pathologists led by Tracy Ann Williams, and published in J Clin Endocrinol Metab, 2021. This article will elaborates on the key points in the consensus to advance the understanding and overall improve clinical mangement of UPA.

Abstract: To explore the role of interleukin(IL)-6 in the process of liver regeneration after acetaminophen(APAP)-induced acute liver injury(ALI) throughin vitroexperiments. Methods: In vitroexperiments, AML12 cell lines which originated from normal mice hepatocytes were cultured and treated with different concentrations of APAP drugs and IL-6 neutralizing antibody(IL-6 Ab). CCK-8 method was used to detect cell viability and screen out the appropriate drug effects concentration. The IL-6 concentration was measured by ELISA. Western blot was used to detect the expression levels of liver regeneration-related proteins such as PCNA, CyclinD1, and HGF. The mRNA levels of IL-6, PCNA and CyclinD1 were measured by qRT-PCR. Datas were analyzed by GraphPad Prism 8.0 software. Results: Based on the CCK-8 data, the optimal drug concentration of 5 mmol/L APAP was selected for modeling and 0.01 μg/ml IL-6 Ab acting cells. The IL-6 concentration was 0, 1.794, 2.264, 1.658, 1.086 pg/ml at 0, 4, 12, 24, 48 h, respectively, measured by ELISA kit. Western blot results showed that compared with other time points after APAP administration on AML12 cells, the protein levels of CyclinD1 was the highest at 4 h, PCNA and HGF were the highest at 12 h(P<0.05). Compared with the 4 h APAP group, the expression of CyclinD1 and p-STAT3 protein in the APAP+IL-6 Ab group decreased(P<0.05); compared with the 12 h APAP group, the expression of PCNA and HGF in the APAP+IL-6 Ab group decreased(P<0.05). The results of qRT-PCR showed that the mRNA levels of IL-6, PCNA, and CyclinD1 in the 4 h APAP group reached the peak(P<0.05);compared with the 4 h APAP group, the PCNA and CyclinD1 levels in the APAP+IL-6 Ab group were reduced(P<0.05). Conclusion IL-6 Ab inhibits STAT3 phosphorylation by neutralizing IL-6 and subsequently inhibits liver regeneration. It is speculated that IL-6 may play a role in promoting liver regeneration after APAP-induced liver injury.

Objective: To verify the applicability of the theory of planned behavior(TPB) in the physical exercise behaviors of rural adolescents in Sichuan Province, and to explore the possible influencing factors of physical exercise behaviors, and to provide a theoretical basis for further effective intervention measures. Methods: A total of 2 302 students were selected from grade seven and grade ten of two rural middle schools in Zizhong, Sichuan Province. The survey was conducted with a structured questionnaire. Using TPB as the research framework and basis, the structural equation model was constructed for analysis. Results: Lack of physical exercise was 1 527(66.3%).Physical exercise behavior was statistically different among schools, grades(t=-7.40，-2.90，10.90,P<0.05)， and genders. Based on TPB, the structural equation model was established and corrected to obtain the revised model, and the fitting index GFI=0.93, CFI=0.94, NFI=0.94, TLI=0.93, IFI=0.94,RMSEA=0.07, indicating the model fitted good. Exercise intention directly affected exercise behaviors. The standardized effect was 0.45(95%CI=0.39-0.52). Subjective norms and perceived power were the main two mediators of the relationship between value evaluation and exercise intention. The standardized effect values were 0.66(95%CI=0.57-0.73), 0.23(95%CI=0.16-0.93)(P<0.01). Conclusion There is serious lack of physical exercise in rural adolescents in Sichuan Province. TPB has a good applicability for physical exercise in rural adolescents in Sichuan Province. Subjective norm is the most important factors to promote exercise intentions.

ObjectiveTo investigate the role of STAT3 in hepatocyte proliferation after acetaminophen (APAP)-induced hepatocellular injury in mice. MethodsNormal mouse AML12 hepatocytes were cultured in vitro and were stimulated by APAP (1, 2.5, 5, 10, and 20 mmol/L) for 12, 24 or 48 hours, and the hepatocytes treated with an equal volume of phosphate buffered saline were established as control group. After the optimal stimulation concentration and duration of action were screened out, AML12 hepatocytes were treated with AG490 (10, 50, and 100 μmol/L). The CCK-8 assay was used to measure the viability of AML12 hepatocytes; RT-PCR was used to measure the mRNA expression levels of PCNA, CyclinD1, and Ki67 in AML12 hepatocytes, and Western blot was used to measure the protein expression levels of STAT3, p-STAT3, PCNA, and CyclinD1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter 24 and 48 hours of APAP treatment, compared with the control group, all concentration groups had a significant reduction in the viability of AML12 hepatocytes (all P＜0.05), with a viability of 0.717±0.0271 and 0.752±0.0141, respectively, when the concentration of APAP was 2.5 mmol/L, which was significantly different from that in the control group (all P＜0.05) and met the conditions of subsequent experiment. Compared with the control group, the 24-hour APAP (2.5 mmol/L) group had significant reductions in the mRNA expression of PCNA, CyclinD1, and Ki67 (all P＜0.01); compared with the 24-hour APAP group, the 48-hour APAP (2.5 mmol/L) group had significant increases in the mRNA expression of PCNA, CyclinD1, and Ki67 (all P＜0.01); therefore, a model of hepatocyte regeneration after in vitro AML12 hepatocyte injury was established by stimulation with APAP 2.5 mmol/L for 48 hours. After the addition of AG490, there was no significant difference in viability between the control group and the 10 and 50 μmol/L AG490 groups, and the other groups had a significant reduction in viability (all P＜0.01); compared with the APAP group, the AG490 (50 μmol/L)+APAP group and the AG490 (100 μmol/L)+APAP group had a significant reduction in viability (P＜0.01); therefore, 50 μmol/L AG490 was selected as the concentration for subsequent experiment. Compared with the control group, the APAP group had a significant increase in the protein expression level of p-STAT3 (P＜0.01), while the AG490 group and the APAP+AG490 group had a significant reduction (both P＜0.05); compared with the APAP group, the APAP+AG490 group had significant reductions in the protein expression levels of PCNA and CyclinD1 and the mRNA expression levels of PCNA, CyclinD1, and Ki67 (all P＜0.05). ConclusionSTAT3 participates in hepatocyte proliferation after APAP-induced hepatocyte injury in mice, while AG490, as an STAT3 inhibitor, can inhibit hepatocyte proliferation after APAP-induced hepatocyte injury by inhibiting the phosphorylation of STAT3.

Objective: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy as comparing with chemotherapy alone for the first-line treatment of advanced NSCLC (non-small lung cancer). Methods: RCTs (randomized controlled trials) on PD-1/PD-L1 inhibitor combined with chemotherapy compared with chemotherapy alone for the first-line treatment of advanced NSCLC were searched in the PubMed, Cochrane Library, EMbase, EBSCO, Chinese Biomedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), and Chinese Scientific Journal Full-text Database (VIP). RevMan 5.2 software was used for the Meta-analysis. Results: Six RCTs with 3 238 advanced NSCLC patients were included in this study. Meta-analysis showed that the combination therapy group was more effective than the chemotherapy alone group in OS (HR=0.86, 95%CI=0.79~ 0.94, P=0.0006) and PFS (HR=0.81, 95%CI=0.78~0.84, P<0.00001). The incidence of adverse reactions, such as thrombocytopenia of grade 1-5, vomiting, diarrhea, hypothyroidism, hyperthyroidism, rash, pneumonitis, colitis, hepatitis, dysgeusia, hepatitis of grade 3-5 and colitis, in combined treatment group were all higher than those in chemotherapy alone group, the differences were statistically significant (P<0.01 or P<0.05). Conclusions: Compared with chemotherapy alone, PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the OS and PFS of patients with advanced NSCLC in the first-line treatment, while the overall incidence of adverse reactions is higher than chemotherapy.