Objective To investigate the differences in Mandarin vowel space area(VSA)across geographic regions and genders.Methods Healthy college students residing in Beijing(62 cases,32 males and 30 females)and Shanghai(62 cases,32 males and 30 females)were selected to study the Mandarin VSA with six Chinese vowels(/a/,/e/,/i/,/u/,/o/,/ü/,and the short text Vacation)as the corpus,respectively.Results The differences in VSA between genders were extremely significant(P＜0.001),and the VSA of females was significantly larger than that of males.Simple effect tests for speech material and region showed that when the speech material was con-tinuous speech,the VSAs of Beijing and Shanghai subjects showed no significant difference,but when the speech material was unitary speech,the VSAs of Shanghai subjects were significantly larger than those of Beijing subjects(P=0.003,P＜0.01).Conclusion The VSAs of female adults were larger than those of male adults,and the front vowels of females were more fronted and the back vowels were more backward.The differences produced by different regions based on the Mandarin system of pronunciation were not significant.

Diabetes mellitus is the third most prevalent disease worldwide,following cardiovascular diseases and cancer.There is no obvious symptom in the early stage of diabetes mellitus.However,in the middle and late stages,diabetes mellitus may lead to severe clinical complications such as diabetic cardiomyopathy,kidney disease,retinopathy,or neuropathy,the primary causes for diabetes-related deaths.Therefore,the early diagnosis and treatment of diabetes mellitus are of practical significance.Compared with traditional diagnostic methods including fasting blood-glucose and oral glucose tolerance tests,the measurement of glycated hemoglobin serves as a gold standard for evaluating long-term blood glucose control,due to the relative stability of glycated hemoglobin under a period of dietary and daily practice.Ear-ly treatment of diabetes mellitus may significantly improve the prognosis of patients and enhance the overall therapeutic out-come.Diet control,physical exercise,medication,as well as psychological and social supports are critical for the treat-ment of diabetes mellitus.To date,the therapeutic methods for diabetes mellitus have been constantly enriching,along with promoted drug design and development.Some emerging technologies,such as therapies using antibodies or stem cells,have been applied to treat diabetes mellitus.Hereby the latest progress in the prevention and treatment of diabetes mellitus was comprehensively reviewed,and the application of antibodies was discussed,which may provide insights into the research and development of antibody drugs for chronic human diseases including diabetes mellitus.

Hemoglobin, the principal protein in red blood cells, is crucial for oxygen transport in the bloodstream. The quantification of hemoglobin concentration is indispensable in medical diagnostics and health management, which encompass the diagnosis of anemia and the screening of various blood disorders. Immunological methods, based on antigen-antibody interactions, are distinguished by their high sensitivity and accuracy. Consequently, it is necessary to develop hemoglobin-specific antibodies characterized by high specificity and affinity to enhance detection accuracy. In this study, we immunized a Bactrian camel (Camelus bactrianus) with human hemoglobin and subsequently constructed a nanobody library. Utilizing a solid-phase screening method, we selected nanobodies and evaluated the binding activity of the screened nanobodies to hemoglobin. Initially, human hemoglobin was used to immunize a Bactrian camel. Following four immunization sessions, blood was withdrawn from the jugular vein, and a nanobody library with a capacity of 2.85×10⁸ colony forming units (CFU) was generated. Subsequently, ten hemoglobin-specific nanobody sequences were identified through three rounds of adsorption-elution-enrichment assays, and these nanobodies were subjected to eukaryotic expression. Finally, enzyme-linked immunosorbent assay and biolayer interferometry were employed to evaluate the stability, binding activity, and specificity of these nanobodies. The results demonstrated that the nanobodies maintained robust binding activity within the temperature range of 20-40 ℃ and exhibited the highest binding activity at pH 7.0. Furthermore, the nanobodies were capable of tolerating a 10% methanol solution. Notably, among the nanobodies tested, VHH-12 displayed the highest binding activity to hemoglobin, with a half maximal effective concentration (EC₅₀) of 10.63 nmol/L and a equilibrium dissociation constant (K_D) of 2.94×10^-7 mol/L. VHH-12 exhibited no cross-reactivity with a panel of eight proteins, such as ovalbumin and bovine serum albumin, while demonstrating partial cross-reactivity with hemoglobin derived from porcine, goat, rabbit, and bovine sources. In this study, a hemoglobin-specific high-affinity nanobody was successfully isolated, demonstrating potential applications in disease diagnosis and health monitoring.
Animals ; Camelus/immunology* ; Single-Domain Antibodies/immunology* ; Hemoglobins/immunology* ; Humans ; Peptide Library

Objective To investigate the differences in Mandarin vowel space area(VSA)across geographic regions and genders.Methods Healthy college students residing in Beijing(62 cases,32 males and 30 females)and Shanghai(62 cases,32 males and 30 females)were selected to study the Mandarin VSA with six Chinese vowels(/a/,/e/,/i/,/u/,/o/,/ü/,and the short text Vacation)as the corpus,respectively.Results The differences in VSA between genders were extremely significant(P＜0.001),and the VSA of females was significantly larger than that of males.Simple effect tests for speech material and region showed that when the speech material was con-tinuous speech,the VSAs of Beijing and Shanghai subjects showed no significant difference,but when the speech material was unitary speech,the VSAs of Shanghai subjects were significantly larger than those of Beijing subjects(P=0.003,P＜0.01).Conclusion The VSAs of female adults were larger than those of male adults,and the front vowels of females were more fronted and the back vowels were more backward.The differences produced by different regions based on the Mandarin system of pronunciation were not significant.

Diabetes mellitus is the third most prevalent disease worldwide,following cardiovascular diseases and cancer.There is no obvious symptom in the early stage of diabetes mellitus.However,in the middle and late stages,diabetes mellitus may lead to severe clinical complications such as diabetic cardiomyopathy,kidney disease,retinopathy,or neuropathy,the primary causes for diabetes-related deaths.Therefore,the early diagnosis and treatment of diabetes mellitus are of practical significance.Compared with traditional diagnostic methods including fasting blood-glucose and oral glucose tolerance tests,the measurement of glycated hemoglobin serves as a gold standard for evaluating long-term blood glucose control,due to the relative stability of glycated hemoglobin under a period of dietary and daily practice.Ear-ly treatment of diabetes mellitus may significantly improve the prognosis of patients and enhance the overall therapeutic out-come.Diet control,physical exercise,medication,as well as psychological and social supports are critical for the treat-ment of diabetes mellitus.To date,the therapeutic methods for diabetes mellitus have been constantly enriching,along with promoted drug design and development.Some emerging technologies,such as therapies using antibodies or stem cells,have been applied to treat diabetes mellitus.Hereby the latest progress in the prevention and treatment of diabetes mellitus was comprehensively reviewed,and the application of antibodies was discussed,which may provide insights into the research and development of antibody drugs for chronic human diseases including diabetes mellitus.

Low-intensity transcranial ultrasound stimulation(LITUS),a high-resolution and safe neuromodulation technique,holds great promise as a treatment option for alleviating both motor and non-motor symptoms in Parkinson disease. This article presents a comprehensive overview of the application of LITUS in the rehabilitation of Parkinson disease from the aspects of the parameters,classification,efficacy,and mechanism of LITUS.

As the major part of mesencephalic locomotion region, pedunculopontine tegmental nucleus (PPN) participates in motor initiation, rhythmic and speed regulation. In addition, PPN is regarded as a novel deep brain stimulation target for patients with Parkinson′s disease due to its dramatic effect on the gait disturbance and postural instability. However, PPN also has an important role in muscle tone control and dystonia. This review is aimed at summarizing the involvement of PPN in dystonia, providing fundamental for targeting PPN for treatment of dystonia in the future.

To explore the process management strategies of standardized residency training based on the development of information management platform, combining with the management practices, this study has sorted out and analyzed process management contents, and integrated process management concepts and contents into the development of information management platform. The development of information management platform taking the process management as the core has contributed to the update and implementation of standardized residency training policies, building of a multi-role interactive bridge, guarantee of information accuracy, and promotion of the construction of quality assurance system, thus providing an effective tool to ensure the quality of training, which is of great significance to cultivate outstanding physicians.

Parkinson′s disease is a neurodegenerative disease characterized by bradykinesia, resting tremor, and hypermyotonia. Its pathological features are the loss of nigra dopamine neurons and the abnormal aggregation of α-synuclein, and there is currently no treatment that blocks the progression of the disease. Gene therapy, by increasing the expression of neurotrophic factors and increasing levels of neurotransmitters, may slow, terminate, or even reverse the progression of the disease, so it gets more attention. This article reviews the progress of registered clinical research on gene therapy for Parkinson′s disease.

Objective To analyze the acoustic features of patients with Parkinson's disease (PD),and to explore the correlation between the acoustic features and the severity and course of disease.Methods Fifty-two patients with PD from the Tongji Hospital Affiliated to Tongji Medical University and the Ninth People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University from August to December 2015 were enrolled into this study.Thirty-two age-matched healthy people served as control group.PD patients were tested with Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr (H-Y) staging.And all the patients were tested with Mini-Mental State Examiantion (MMSE) and Voice Handicap Index (VHI).The voice samples of all subjects were collected and the frequency perturbation (jitter),amplitude perturbation (shimmer),and harmonic-to-noise ratio (NHR) were analyzed using a vocal assessment.Fundamental frequency (F0),standard deviation of fundamental frequency (SDF0) and formant ratio (F2i/F2u) were analyzed using a real-time speech measuring instrument.The acoustic parameters of the two groups were compared and the correlation between the parameters of the patients and the disease and course of disease was analyzed.Results Subjective assessment using VHI showed a total of 24 VHI abnormalities (46％) in the PD group,including 13 males (54％),11 females (46％).No VHI abnormalities were found in the control group.Among the parameters analyzed by objective acoustic method,compared with the control group (female/a/1.43(1.19,1.92),/i/3.39(1.49,9.85),/u/1.46(1.23,3.85);male/a/1.06(0.92,1.89),/u/1.30(1.07,1.64)),the SDF0 of the three vowels of the female patients in the PD group (/a/2.99(1.81,4.12),Z=5.429,P＜0.01;/i/10.89(5.47,22.20),Z=8.487,P＜0.01;/u/5.16(3.75,7.80),Z=7.138,P＜0.01) and /a/ and /u/ of the male patients in the PD group (/a/2.16(1.73,2.94),Z=4.858,P=0.002;/u/3.70(2.41,5.43),Z=7.664,P＜0.01) were significantly increased,and the F2i/F2u in the PD group (male 1.96±0.84,female 1.81± 1.14) was lower than that in the control group (male 3.48±0.70,female 4.14± 1.08),and the difference was statistically significant (t=-6.669,-6.844,P＜0.01).There were no statistically significant differences in frequency perturbation,amplitude perturbation,harmonic noise ratio and fundamental frequency.Only the fundamental frequency standard deviation of the sound parameters used in the study was correlated with the disease course of PD patients.After the severity of the disease was assessed by H-Y staging,the frequency perturbation (jitter),amplitude perturbation (shimmer) in the middle and late stage patients were higher than those in the early stage patients,and the difference of frequency perturbation in the three vowels was statistically significant,and the difference of amplitude perturbation in the vowels/i/and/u/was statistically significant.No correlation was found between the acoustic parameters and UPDRS score.Conclusions Consonance disorders are common in PD patients,and the changes in acoustic parameters are mainly manifested as the increase in the SDF0 and the decrease in the F2i/F2u.Acoustic parameters can be used as an effective indicator to evaluate the condition and course of PD patients,and further language tasks need to be added to clarify.