The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

The life view of physique-qi-spirit trinity is the core theory for explaining the physiological activities of human body and the evolution of disease pathology in traditional Chinese medicine(TCM),and will bring about an overview of TCM tumorigenesis.This paper explores the biological basis of tumor from the perspective of disorders of physique,qi and spirit:there is a correlation between qi-physique transformation and energy and substance metabolism,and between spirit-emotion and neuromodulation;the nerve-metabolism pathway contributes to partial biological basis of tumor from the perspective of disorders of physique,qi and spirit.Furthermore,it puts forward the strategies for prevention and treatment with TCM through the simultaneous regulation of physique,qi and spirit:eliminating the mass to inhibit the tumor,and improving physique to preserve life in the view of treating physique;replenishing qi to strengthen the body,and ventilating qi to remove toxins in the view of treating qi;regulating the spirit to treat cancer through comprehensive therapy in the view of treating spirit.The exploration on the biological basis of tumor from the perspective of disorders of physique,qi and spirit will further embody the unique advantages of TCM theories in understanding malignant tumors,and will provide useful references for the model of synergistic prevention and treatment of malignant tumors with TCM.

Objective:To elucidate the complete genomic characteristics of the Akabane virus (AKV) DHL10M117 strain and the Tibet orbivirus (TIBOV) DH10M1019 strain, isolated from mosquito specimens collected in 2010 from Dehong prefecture, Yunnan province.Methods:The complete RNA virus sequences were obtained using metatranscriptomics and high-throughput sequencing.Results:The complete genome sequences of the DHL10M117 strain, consisting of the S, M, and L gene segments with lengths of 856 bp, 4 309 bp, and 6 869 bp, respectively, were acquired. Phylogenetic analysis indicated that the DHL10M117 strain is an AKV strain, closely related to the AKV strain DHL10M110, isolated from Yunnan. The S and M segment phylogenetic trees revealed that the strain is closely related to AKV strains circulating in southern China and Japan, and distantly related to strains from Australia, suggesting that this strain belongs to the Asian lineage with distinct regional characteristics. Homology analysis confirmed that the gene sequences of the S, M, and L segments of the DHL10M117 strain showed 100% nucleotide and amino acid identity with the DHL10M110 strain. Additionally, the complete genome sequences of the DH10M1019 strain, comprising ten gene segments (Seg-1 to Seg-10) with lengths of 3 950 bp, 2 904 bp, 2 769 bp, 1 978 bp, 1 772 bp, 1 638 bp, 1 165 bp, 1 142 bp, 1 103 bp, and 832 bp respectively, were obtained. Phylogenetic analysis showed that DH10M1019 is a TIBOV strain, with eight gene segments (Seg-1 to Seg-4, Seg-6, Seg-8 to Seg-10) clustering with known strains in the same major branch, while Seg-5 and Seg-7 formed distinct branches, independent of known reference strains, suggesting that DH10M1019 may represent a new serotype of TIBOV.Conclusions:Through complete genome sequence analysis, it was confirmed that DHL10M117 and DH10M1019 are AKV and TIBOV, which provided a scientific basis for the epidemiological characterisation, pathogenicity analysis and investigation of the two viruses.

Objective:The complete genome sequence characteristics of Quang Binh virus (QBV) and Manglie virus (MaV) isolated from mosquitoes in Daluo Town, Menghai county.Methods:Mosquitoes collected in Daluo Town, Menghai county in July 2012 were used for virus isolation. The nucleic acid was extracted from the supernatant of Aedes albopictus cell line (C6/36) showing cytopathic effect (CPE) positivity, and was sent to a company for sequencing after library construction. Phylogenetic and nucleotide/amino acid sequence similarity analysis was performed using DNAStar, Maff, and other softwares.Results:RNA libraries of strains BNDL1205 and BNDL1227 yielded 67 336 692 and 61 259 266 qualified gene sequences (reads) respectively. After assembly and alignment, sequences of lengths 10 865 bp and 10 864 bp were obtained. Sequence analysis indicated that they belong to QBV, with strains BNDL1205 and BNDL1227 clustering with QBV (strain VN180) isolated from Vietnam on the same evolutionary branch, sharing nucleotide similarity of 84.2% and 84.1%, and amino acid similarity of 94.6% and 94.4% respectively. RNA library of strain BNDL1223 yielded 48 622 610 qualified reads. After assembly and alignment, three gene fragments (Contigs) matched MaV. Further merging using SeqMan produced a complete nucleotide sequence of 9 219 bp. Analysis revealed that strain BNDL1223 is closely related to MaV isolated in Yunnan in 2018, sharing nucleotide similarity of 97.8% and amino acid similarity of 99.2%.Conclusions:During the investigation of arboviruses in mosquitoes in Daluo Town, Menghai county, three strains of viruses were identified: 2 strains of QBV and 1 strain of MaV. Local mosquitoes play a significant role in the transmission of QBV and MaV, necessitating enhanced monitoring and detection of local vector mosquitoes.

Objective:To elucidate the complete genomic characteristics of the Akabane virus (AKV) DHL10M117 strain and the Tibet orbivirus (TIBOV) DH10M1019 strain, isolated from mosquito specimens collected in 2010 from Dehong prefecture, Yunnan province.Methods:The complete RNA virus sequences were obtained using metatranscriptomics and high-throughput sequencing.Results:The complete genome sequences of the DHL10M117 strain, consisting of the S, M, and L gene segments with lengths of 856 bp, 4 309 bp, and 6 869 bp, respectively, were acquired. Phylogenetic analysis indicated that the DHL10M117 strain is an AKV strain, closely related to the AKV strain DHL10M110, isolated from Yunnan. The S and M segment phylogenetic trees revealed that the strain is closely related to AKV strains circulating in southern China and Japan, and distantly related to strains from Australia, suggesting that this strain belongs to the Asian lineage with distinct regional characteristics. Homology analysis confirmed that the gene sequences of the S, M, and L segments of the DHL10M117 strain showed 100% nucleotide and amino acid identity with the DHL10M110 strain. Additionally, the complete genome sequences of the DH10M1019 strain, comprising ten gene segments (Seg-1 to Seg-10) with lengths of 3 950 bp, 2 904 bp, 2 769 bp, 1 978 bp, 1 772 bp, 1 638 bp, 1 165 bp, 1 142 bp, 1 103 bp, and 832 bp respectively, were obtained. Phylogenetic analysis showed that DH10M1019 is a TIBOV strain, with eight gene segments (Seg-1 to Seg-4, Seg-6, Seg-8 to Seg-10) clustering with known strains in the same major branch, while Seg-5 and Seg-7 formed distinct branches, independent of known reference strains, suggesting that DH10M1019 may represent a new serotype of TIBOV.Conclusions:Through complete genome sequence analysis, it was confirmed that DHL10M117 and DH10M1019 are AKV and TIBOV, which provided a scientific basis for the epidemiological characterisation, pathogenicity analysis and investigation of the two viruses.

Objective:The complete genome sequence characteristics of Quang Binh virus (QBV) and Manglie virus (MaV) isolated from mosquitoes in Daluo Town, Menghai county.Methods:Mosquitoes collected in Daluo Town, Menghai county in July 2012 were used for virus isolation. The nucleic acid was extracted from the supernatant of Aedes albopictus cell line (C6/36) showing cytopathic effect (CPE) positivity, and was sent to a company for sequencing after library construction. Phylogenetic and nucleotide/amino acid sequence similarity analysis was performed using DNAStar, Maff, and other softwares.Results:RNA libraries of strains BNDL1205 and BNDL1227 yielded 67 336 692 and 61 259 266 qualified gene sequences (reads) respectively. After assembly and alignment, sequences of lengths 10 865 bp and 10 864 bp were obtained. Sequence analysis indicated that they belong to QBV, with strains BNDL1205 and BNDL1227 clustering with QBV (strain VN180) isolated from Vietnam on the same evolutionary branch, sharing nucleotide similarity of 84.2% and 84.1%, and amino acid similarity of 94.6% and 94.4% respectively. RNA library of strain BNDL1223 yielded 48 622 610 qualified reads. After assembly and alignment, three gene fragments (Contigs) matched MaV. Further merging using SeqMan produced a complete nucleotide sequence of 9 219 bp. Analysis revealed that strain BNDL1223 is closely related to MaV isolated in Yunnan in 2018, sharing nucleotide similarity of 97.8% and amino acid similarity of 99.2%.Conclusions:During the investigation of arboviruses in mosquitoes in Daluo Town, Menghai county, three strains of viruses were identified: 2 strains of QBV and 1 strain of MaV. Local mosquitoes play a significant role in the transmission of QBV and MaV, necessitating enhanced monitoring and detection of local vector mosquitoes.

Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees (P<0.001), and the axial length of the right/left eye increased in various degrees (P<0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant (P<0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m² was the protective factor of eye axis length (HR=0.778, 95%CI: 0.659-0.918, P=0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length (HR=0.685, 95%CI: 0.592-0.793, P<0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length (HR=0.456, 95%CI: 0.534-0.761, P<0.001; HR=0.794, 95%CI: 0.705-0.895, P<0.001; HR=0.690, 95%CI: 0.619-0.768, P<0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length (HR=1.528, 95%CI: 1.018-2.293, P=0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length (HR=0.542, 95%CI: 0.404-0.726, P<0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length (HR=0.820, 95%CI: 0.698-0.965, P=0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter (HR=0.638, 95%CI: 0.534-0.761, P<0.001; HR=0.911, 95%CI: 0.848-0.978, P=0.011; HR=0.750, 95%CI: 0.702-0.801, P<0.001). The average illumination of desktop 500- lx was a protective factor of a diopter (HR=0.855, 95%CI: 0.763-0.958, P=0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.
Humans ; Mydriasis ; Myopia/prevention & control* ; Refraction, Ocular ; Students ; Surveys and Questionnaires ; Schools

OBJECTIVES: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis. METHODS: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis. RESULTS: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05). CONCLUSIONS Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.
Child ; Humans ; Infant ; Adrenocorticotropic Hormone/therapeutic use* ; Spasms, Infantile/drug therapy* ; Treatment Outcome ; Seizures ; Electroencephalography/adverse effects* ; Spasm/drug therapy*

Chronic cough is caused by low levels of heat, mechanical or chemical exposure, which is characterized by the disorders of channels and receptors in neuroregulation such as the peripheral and central nerves. Potential regulatory targets of peripheral nerves include P2X3 receptors and transient receptor potential channels, while potential regulatory targets of central nerves include voltage-gated sodium channels, neurokinin-1 receptors, α-7acetylcholine receptors and gamma aminobutyric acid receptors. This paper focuses on the principle and clinical research evidence of several ongoing targeted therapy strategies, in order to provide new ideas for the development of drugs for the treatment of chronic cough.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome