BACKGROUND:Stroboscopic visual training can force sensory reweighting to restore the original weights by increasing sensitivity to proprioceptive information,which may be an effective method to improve proprioception. OBJECTIVE:To determine the effects of balance training in three conditions,low frequency,high frequency and normal vision,on ankle proprioception in patients with chronic ankle instability. METHODS:Thirty-six patients with chronic ankle instability recruited from the students of Southwest Medical University were randomly assigned to a low-frequency vision training group,a high-frequency vision training group,and a normal vision training group,with 12 subjects in each group.Subjects in the three groups underwent progressive hop stabilization and balance training,in which the low-frequency vision training group and the high-frequency vision training group wore stroboscopic spectacles during the training,with a stroboscopic frequency of 1.75 and 5 Hz,respectively.The training in each group was performed three times a week for 4 consecutive weeks.Assessments,including ankle proprioception,ankle stability self-assessment and dynamic postural stability,were performed before training and within 1 week after the completion of training. RESULTS AND CONCLUSION:There was a significant main effect of time factor in ankle proprioception(P<0.05).Compared with the pre-training period,subjects in the low-frequency vision training group and the high-frequency vision training group showed significant improvement in ankle proprioception after 4 weeks of training(P<0.05);and subjects in the low-frequency vision training group showed a significant improvement in ankle proprioception compared with that of the normal vision training group after 4 weeks of training(P<0.05).There were significant main effects of time factor and group×time interaction in ankle proprioception(P<0.05).Compared with the pre-training period,the ankle stability self-assessment in all three groups was improved after 4 weeks of training(P<0.05).And the ankle stability self-assessment in high-frequency visual training group was higher than that in normal vision training group after 4 weeks of training(P<0.05).Compared with the pre-training period,subjects in the low-frequency vision training group and the high-frequency vision training group showed significant improvements in forward dynamic postural stability,posteromedial dynamic postural stability,and posterolateral dynamic postural stability after 4 weeks of training(P<0.05),while in the normal vision training group,forward dynamic postural stability and posterolateral dynamic postural stability were significantly improved after 4 weeks of training(P≤0.05).To conclude,balance training under stroboscopic visual conditioning improves proprioception,ankle stability self-assessment,and dynamic postural stability in patients with chronic ankle instability regardless of frequency.

Objective:To identify and observe the pathogenic genes and clinical phenotypes of a family with a special platelet phenotype, Hermansky-Pudlak syndrome type 6 (HSP6).Methods:A retrospective clinical study. In November 2019, one proband and three family members from six HSP families who visited Henan Eye Hospital were included in the study. The child's medical history and family history were inquired in detail. The proband and all family members underwent best corrected visual acuity (BCVA), fundus color photography, frequency-domain optical coherence tomography, and general physical examination. The proband underwent platelet transmission electron microscopy (PTEM) and colonoscopy. Peripheral venous blood was collected from the proband, her parents and younger brother, and genomic DNA was extracted. Whole exome sequencing (WES) was used to screen pathogenic genes and their loci. Bioinformatics analysis determines the pathogenicity of gene variation sites. Fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to verify the related variations.Results:The proband (Ⅱ-1) was a 7-year-old female. The BCVA in both eyes was 0.1, who exhibited mild horizontal nystagmus and iris depigmentation. Fundus examination revealed obvious depigmentation and an underdeveloped fovea centralis. At the age of 7, the patient underwent colonoscopy due to acute gastrointestinal bleeding. A polyp approximately 5 mm in size was found on the floor of the sigmoid colon, with erosion and mucosal leukoplakia on its surface. PTEM showed that the number of platelet dense granules was normal, but the nuclei were small or exhibited low compactness. The skin on both lower legs showed pigmentation. The clinical phenotypes of the proband’s parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) showed no obvious abnormalities. WES revealed that the proband carried compound heterozygous variants in exon 1 of the HPS6 gene: c.60_64dup (p.L22fs) (M1) and c.1147_1148del (p.L383fs) (M2). The mother carried the M1 variant, while the father and younger brother carried the M2 variant. Bioinformatics analysis predicted that both variants were pathogenic. RT-qPCR results showed that, compared with the relative expression level of HPS6 wt mRNA, the relative expression levels of HPS6 L22fs and HPS6 L383fs mRNA were significantly decreased ( t = 3.549, 4.560; P<0.05). Western blot analysis demonstrated that the HPS6 L383fs protein was truncated, whereas the HPS6 L22fs protein was not detected. Conclusions:This family is a special HPS6 with a normal number of dense platelet granules. The compound heterozygous variations of M1 and M2 in the HPS6 gene are pathogenic genes in this family.

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

Background and Aims:Secondary hyperparathyroidism(SHPT)is a common and difficult-to-treat complication of chronic kidney disease(CKD),significantly impairing patients'quality of life and prognosis.For patients who respond poorly to medical therapy,surgical intervention remains an effective treatment option.This study aimed to evaluate the clinical efficacy and safety of total parathyroidectomy with forearm autotransplantation(tPTX+AT)in the treatment of CKD-related SHPT.Methods:A retrospective analysis was conducted on 40 patients with CKD complicated by SHPT who underwent tPTX+AT in Gaozhou People's Hospital between January 2020 and June 2023.Changes in intact parathyroid hormone(iPTH),serum phosphorus,calcium,alkaline phosphatase(ALP),and bone mineral density(BMD)were recorded preoperatively and at multiple postoperative time points.Postoperative symptom relief,complications,and follow-up outcomes were also analyzed.Results:A total of 158 parathyroid glands were removed during surgery.Among the patients,38 had four glands successfully excised,while two had only three glands removed.After operation,levels of iPTH,phosphorus,calcium,and ALP decreased significantly compared to preoperative values(all P<0.05),and BMD increased significantly at 3 months(P<0.05).Symptoms such as bone pain,pruritus,and restless leg syndrome improved markedly by 3 months postoperatively(all P<0.05).Hypocalcemia occurred in 34 cases(85.0%);one patient experienced transient recurrent laryngeal nerve injury and one had superior laryngeal nerve injury,both of which resolved after treatment.The two patients who had only three glands removed exhibited persistent SHPT postoperatively,with iPTH levels of 457 pg/mL and 609 pg/mL,respectively.Although their symptoms improved partially,the condition was medically controlled without the need for reoperation.Conclusion:tPTX+AT can effectively correct mineral metabolism disorders and improve BMD and clinical symptoms in SHPT patients.The procedure achieves a high rate of complete gland resection and stable autograft function.Although postoperative hypocalcemia is common,overall complications are manageable.This surgical approach is safe and effective for the treatment of refractory SHPT.

Background and Aims:Secondary hyperparathyroidism(SHPT)is a common and difficult-to-treat complication of chronic kidney disease(CKD),significantly impairing patients'quality of life and prognosis.For patients who respond poorly to medical therapy,surgical intervention remains an effective treatment option.This study aimed to evaluate the clinical efficacy and safety of total parathyroidectomy with forearm autotransplantation(tPTX+AT)in the treatment of CKD-related SHPT.Methods:A retrospective analysis was conducted on 40 patients with CKD complicated by SHPT who underwent tPTX+AT in Gaozhou People's Hospital between January 2020 and June 2023.Changes in intact parathyroid hormone(iPTH),serum phosphorus,calcium,alkaline phosphatase(ALP),and bone mineral density(BMD)were recorded preoperatively and at multiple postoperative time points.Postoperative symptom relief,complications,and follow-up outcomes were also analyzed.Results:A total of 158 parathyroid glands were removed during surgery.Among the patients,38 had four glands successfully excised,while two had only three glands removed.After operation,levels of iPTH,phosphorus,calcium,and ALP decreased significantly compared to preoperative values(all P<0.05),and BMD increased significantly at 3 months(P<0.05).Symptoms such as bone pain,pruritus,and restless leg syndrome improved markedly by 3 months postoperatively(all P<0.05).Hypocalcemia occurred in 34 cases(85.0%);one patient experienced transient recurrent laryngeal nerve injury and one had superior laryngeal nerve injury,both of which resolved after treatment.The two patients who had only three glands removed exhibited persistent SHPT postoperatively,with iPTH levels of 457 pg/mL and 609 pg/mL,respectively.Although their symptoms improved partially,the condition was medically controlled without the need for reoperation.Conclusion:tPTX+AT can effectively correct mineral metabolism disorders and improve BMD and clinical symptoms in SHPT patients.The procedure achieves a high rate of complete gland resection and stable autograft function.Although postoperative hypocalcemia is common,overall complications are manageable.This surgical approach is safe and effective for the treatment of refractory SHPT.

Objective:To identify and observe the pathogenic genes and clinical phenotypes of a family with a special platelet phenotype, Hermansky-Pudlak syndrome type 6 (HSP6).Methods:A retrospective clinical study. In November 2019, one proband and three family members from six HSP families who visited Henan Eye Hospital were included in the study. The child's medical history and family history were inquired in detail. The proband and all family members underwent best corrected visual acuity (BCVA), fundus color photography, frequency-domain optical coherence tomography, and general physical examination. The proband underwent platelet transmission electron microscopy (PTEM) and colonoscopy. Peripheral venous blood was collected from the proband, her parents and younger brother, and genomic DNA was extracted. Whole exome sequencing (WES) was used to screen pathogenic genes and their loci. Bioinformatics analysis determines the pathogenicity of gene variation sites. Fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to verify the related variations.Results:The proband (Ⅱ-1) was a 7-year-old female. The BCVA in both eyes was 0.1, who exhibited mild horizontal nystagmus and iris depigmentation. Fundus examination revealed obvious depigmentation and an underdeveloped fovea centralis. At the age of 7, the patient underwent colonoscopy due to acute gastrointestinal bleeding. A polyp approximately 5 mm in size was found on the floor of the sigmoid colon, with erosion and mucosal leukoplakia on its surface. PTEM showed that the number of platelet dense granules was normal, but the nuclei were small or exhibited low compactness. The skin on both lower legs showed pigmentation. The clinical phenotypes of the proband’s parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) showed no obvious abnormalities. WES revealed that the proband carried compound heterozygous variants in exon 1 of the HPS6 gene: c.60_64dup (p.L22fs) (M1) and c.1147_1148del (p.L383fs) (M2). The mother carried the M1 variant, while the father and younger brother carried the M2 variant. Bioinformatics analysis predicted that both variants were pathogenic. RT-qPCR results showed that, compared with the relative expression level of HPS6 wt mRNA, the relative expression levels of HPS6 L22fs and HPS6 L383fs mRNA were significantly decreased ( t = 3.549, 4.560; P<0.05). Western blot analysis demonstrated that the HPS6 L383fs protein was truncated, whereas the HPS6 L22fs protein was not detected. Conclusions:This family is a special HPS6 with a normal number of dense platelet granules. The compound heterozygous variations of M1 and M2 in the HPS6 gene are pathogenic genes in this family.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective To analyze the chemical components of Xiaoshi Lidan pills by using UPLC-MS/MS and explore the mechanism of Xiaoshi Lidan pills in the treatment of cholelithiasis through network pharmacology and molecular docking techniques.Methods The pharmacologically active components of Xiaoshi Lidan pills were analyzed through UPLC-MS/MS and compared with standard references.Potential targets of these components were obtained by searching the TCMSP and ETCM databases,and disease-related targets for cholelithiasis were identified using the DisGeNET database.The overlapping targets were used to construct a protein-protein interaction(PPI)network in the String database,and a"drug-component-target"network was built using Cytoscape 3.9.1.GO and KEGG enrichment analyses were performed for the core targets.Finally,the top 5 compounds with strong activity were selected as ligands for molecular docking with the screened disease target genes.The anti-inflammatory activity was verified by RAW264.7 cells,and the mRNA expression of TNF-a and other inflammatory factors was detected by RT-PCR.Results UPLC-MS/MS identified 30 compounds in Xiaoshi Lidan pills,among which baicalin,quercetin,wogonin,baicalein-7-O-glucuronide,and emodin were identified as key components of Xiaoshi Lidan pills.Network pharmacology identified 107 targets associated with cholelithiasis,with Alb,TP53,ESR1,TNF,and INS identified as core targets.GO analysis indicated the involvement in inflammation response and steroid binding,while KEGG pathways were primarily related to lipid metabolism,atherosclerosis,and the TNF signaling pathway.Molecular docking analysis and anti-inflammatory screening in vitro showed that Xiaoshi Lidan pills exhibited certain anti-inflammatory activity by regulating inflammatory factors such as TNF and inhibiting NO production through baicalein,quercetin,emodin and other components.Conclusion Xiaoshi Lidan pills exerts its therapeutic effect on cholelithiasis by regulating TNF-related pathways through components such as baicalin,thereby inhibiting the inflammatory response.

Objective:To investigate the clinical efficacy of percutaneous kyphoplasty (PKP) assisted by intuitive visual navigation orthopaedic surgery robot in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective analysis was conducted in Peking University Third Hospital from June 2021 to November 2022, 78 patients with OVCF were treated by the intuitive visual navigation orthopaedic surgery robot or freehand surgery with a "C" arm X-ray machine. According to the method of puncture, they were divided into robot group and freehand group. In the robot group, there were 36 cases, including 7 males and 29 females, aged 74.50±5.87 years, 32 cases of single vertebral fractures, 4 cases of double vertebral fractures, 1 case of T 8, 2 cases of T 10, 2 cases of T 11, 11 cases of T 12, 10 cases of L 1, 8 cases of L 2, 2 cases of L 3, 3 cases of L 4, and 1 case of L 5. Bone mineral density T value was -2.94±0.50; In the freehand group, there were 42 cases, including 9 males and 33 females, aged 72.86±8.84 years, 36 cases of single fracture and 6 cases of double fracture, 1 case of T 6, 2 cases of T 7, 3 cases of T 11, 9 cases of T 12, 8 cases of L 1, 9 cases of L 2, 5 cases of L 3, 6 cases of L 4, and 5 cases of L 5. Bone mineral density T value was -3.00±0.50. The effectiveness evaluation indexes of the two groups were compared, which included surgery duration, X-ray fluoroscopy times, hospitalization time, lumbar pain visual analogue scale (VAS), Oswestry disability index (ODI) and height of fractured anterior vertebrae (HFAV). Results:Both groups of patients successfully received surgical treatment. The mean operating time of the robot group was 33.44±2.50 min, which was significantly longer than that of the free hand group, which was 29.69±2.40 min ( t=6.491, P<0.001). Meanwhile, the intraoperative blood loss of the robot group was 3.54±0.89 ml, which was significantly less than that of the freehand group, which was 6.72±1.89 ml ( t=9.110, P<0.001). In terms of radiographic fluoroscopy times, the average of the robot group was 26.81±7.76 times, which was significantly less than the freehand group's 42.61±6.62 times ( t=9.294, P<0.001). The postoperative vertebral front edge height in the free hand group was 18.64±0.32 mm and in the robot group was 18.79±0.36 mm. The difference was not statistically significant ( t=2.673, P=0.067). All patients were followed up for 8.3±2.9 months (range, 6-13 months). The VAS scores of low back pain in the two groups at 1 day and 6 months after operation were significantly improved compared with those before operation ( P<0.05), and there was no significant difference between the two groups in VAS score after operation ( P>0.05). Six months after surgery, the ODI of the free hand group and the robot group were 11.67%±2.13% and 12.11%±2.33%, respectively. The ODI scores of the two groups were significantly lower at 6 months postoperative follow-up than that before surgery, and the postoperative follow-up at all had significant differences compared with that before surgery ( P<0.05), and there was no difference between the two groups in postoperative ODI scores ( P>0.05). No obvious bone cement leakage was found in all patients during operation. Conclusion:Compared with the traditional C-arm X-ray for PKP treatment of OVCF by free hand, intuitive visual navigation orthopedic robot can safely and effectively assist in the completion of the operation process, and has the advantages of less intraoperative blood loss, fewer fluoroscopy times.