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 Following four immunization sessions, blood was withdrawn from the jugular vein, and a nanobody library with a capacity of 2.85×10⁸ colony forming units (CFU) was generated.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

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.

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.

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.

Objective: To explore the current residents training of standardized training program and their attitude towards the program, so as to provide suggestions for optimizing the training system. Methods: Questionnaire surveys were carried out among 1 427 resident physicians from 10 hospitals in 7 provinces and cities between March 2017 to May 2017. The investigation covered demographic information, current work and study, training effect and problems. Statistical description and χ² test were used for analysis. Results: Only 18.08% of the residents in standardized training program considered it as unnecessary, while 80% of them agreed with its effectiveness in improving their clinical skills and humanistic quality. 67.29% of them thought of resignation because of low income and high work pressure. Compared with " double track" residents, those of " double-track integration" complained of lower income and higher workload. Conclusions Chinese residents in standardized training program had a positive attitude towards the training system. However, the measures should be improved to prevent from possible occupational burnout. It is suggested that professionalism and professional identity education be improved, and subjective well-being feeling of residents be focused to avoid burnouts.

Objective To explore the characteristics of trunk muscle activity in persons with Parkinson's disease (PD) in search of better treatments for abnormal posture.Methods Ninety persons with PD of different severity and 8 normal controls were studied using surface electromyography (sEMG).A sixteen-lead sEMG instrument was used to collect sEMG amplitudes from the bilateral thoracic erector spinae,lumbar erector spinae,external oblique and rectus abdominis muscles when the subjects were lying,standing and walking.Results Compared with the control group,a significant increase was observed in the sEMG amplitude of the lumbar erector spinal muscle [(18.56±14.57) μV] and rectus abdominis muscles [(24.00±18.80)μV] of the PD group when lying.Significant relative increases in (P＜0.05),of the external oblique muscles were observed [(27.87± 11.49)μV] when standing (P＜0.05),and in the thoracic erector spinae muscle [(58.74±29.69)μV] and external oblique muscles [(59.01± 25.20) μV] increased when walking (P＜0.05).Compared with the control group,the sEMG activity of the external oblique muscles was significantly elevated in PD patients at Hoehn and Yahr stage 1 to 1.5 when walking.One or more of the trunk muscle groups showed significantly greater activity in the PD patients in Hoehn and Yahr stage 2 or 3 in all three positions.Conclusions The sEMG activities of the extensor and flexor muscles increase simultaneously in PD patients.More trunk muscles are involved in PD patients with higher H-Y grades.These findings provide a neurophysiological basis for the customizaton of rehabilitation therapy for patients with Parkinson's disease and for the precise selection of muscles for botulinum toxin injection.

As a local and effective denervation method,botulinum toxin has been applied in more and more fields.Practitioners who use botulinum toxin should consider the general situation of patients based on the view of effectors,weigh the pros and cons and set reasonable goals before injection,referring to the Chinese expert consensus.

Objective To investigate the effect of insulin-like growth factor 1 antibody (IGF-1Ab) on motor endplate function after injection ofbotulinum toxin A (Btx-A).Methods The total 90 male SD rats were randomly divided into 4 groups:control group,Btx-A group and 2 ug and 20 ug IGF-1Ab groups.In Btx-A and IGF-1Ab groups,a volume of 0.5 U (0.1 mL) Btx-A was intramuscularly injected into a site in the fight gastrocnemius muscle;on day 3,equal volumes (0.1 mL) of IGF-1Ab with a dosage of 2 ug and 20 ug were injected to the 2 ug and 20 ug IGF-1Ab groups respectively at the same site.The gastrocnemius muscle strength and the mean optical density (MOI) value of the positive reaction zone of acetylcholine esterase staining were evaluated at different time points.Results The gastrocnemius muscle strength increased from 12.34±0.16 g before injection to 7.70±0.90 g after injection in the Btx-A group;the gastrocnemius muscle strength decreased in other groups after injection of Btx-A;on day 14,28,42,56 and 70,the muscle strength oflGF-1Ab groups was significantly lower than that of Btx-A group (P＜0.05),and on day 42-70,the value of muscle strength of 20 ug IGF-1Ab group was signficantly lower than that of 2 μg IGF-1Ab group (P＜0.05).The MOI values of the positive reaction zone changed with the same trend.Conclusion IGF-1Ab can suppress the restore of motor endplate function after injection of Btx-A.