OBJECTIVES: To investigate the clinical features and gene mutation characteristics of combined oxidative phosphorylation deficiency type 7 (COXPD7) caused by mutations in the C12orf65 gene, and to enhance the awareness of this disease. METHODS: A child diagnosed with COXPD7 in the Department of Neurology, Children's Hospital Affiliated to Zhengzhou University in 2021 was included, along with 10 patients reported in the literature. All subjects were analyzed for their genotypes and clinical phenotypes. RESULTS: A total of 11 patients with COXPD7 were included, comprising 1 reported in this study and 10 from the literature. Among the 11 patients, 9 had homozygous mutations in the C12orf65 gene, while 2 had compound heterozygous mutations, which were identified as frameshift or nonsense mutations. The age of onset ranged from 1 day to 2 years, and clinical manifestations included optic nerve atrophy and delays in intellectual and motor development. Eight patients exhibited external ophthalmoplegia, and five patients displayed spastic paralysis. Cranial magnetic resonance imaging revealed optic nerve atrophy in all 11 patients, abnormal brainstem signals in 10 patients, and a lactate peak on brainstem magnetic resonance spectroscopy scans in 3 patients. CONCLUSIONS COXPD7 associated with the C12orf65 gene results from homozygous or compound heterozygous mutations, with primary clinical manifestations of optic nerve atrophy and delays in intellectual and motor development. Some patients may also present with spastic paralysis or external ophthalmoplegia. Cranial imaging reveals symmetrical abnormal signals in bilateral basal ganglia and brainstem, and a lactate peak is observed on brainstem magnetic resonance spectroscopy scans.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Oxidative Phosphorylation ; Infant, Newborn

Objective:To investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Objective:To investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Objective:To explore the feasibility and effect of remote medical education model using online film reading training to improve the ability of ophthalmologists in the Xinjiang Uygur Autonomous Region (hereinafter referred to as "Xinjiang Region" ) in diagnosing fundus diseases.Methods:The three-level film reading training system of Xinjiang Production and Construction Corps system division hospital-Corps Hospital-Peking Union Medical College Hospital was established. From June 2022 to January 2023, 4 159 posterior color fundus images were continuously collected from Department of Ophthalmology of Xinjiang Corps Hospital and 4 divisional hospitals in the Corps medical system. Among them, hypertensive retinopathy, diabetic retinopathy, exudative age-related macular degeneration (AMD), atrophic AMD and retinal vein occlusion were 3 073, 651, 43, 186 and 206 cases, respectively. The images were divided into 3 rounds (first, second and last) according to the proportion of diseases. The doctors who participated in the training (hereinafter referred to as the "training") were 15 ophthalmologists from the Corps Hospital of Xinjiang Region and the division hospital of the Corps system. There were 7 male and 8 female. Age was (38.1±4.0) years. The titles of senior, deputy senior, intermediate and junior are 1, 6, 5 and 3 respectively; Bachelor's degree and master's degree are 13 and 2 respectively. The working time of fundus disease specialty was (9.6±3.3) years. The film reading system training was conducted before the first round of labeling, and after each round of film reading, the doctors of Peking Union Medical College Hospital gave feedback and explanation on the film reading results. The diagnostic consistency, sensitivity and specificity were compared by paired sample t test. Spearman or Pearson correlation analysis was conducted between the improvement of diagnostic level and professional title, education, age and working hours of ocular fundus disease. Results:All the participating doctors completed the first, second and last reading. After each round of film reading, the film reading summary was carried out for 2 hours. The average diagnostic agreement rates of participating physicians were 53.0%, 67.0% and 75.0%, respectively. The sensitivity and specificity were 0.38, 0.69, 054 and 0.66, 0.85, 0.96, respectively. There was significant difference between the first and last examination ( P<0.001). The sensitivity of the second reading was significantly higher than that of the first reading, and the sensitivity of the last reading was significantly lower than that of the second reading, with statistical significance ( P<0.05). The specificity of the second reading was significantly higher than that of the first reading, and the last reading was significantly higher than that of the second reading, with statistical significance ( P<0.05). There was no significant correlation ( P>0.05) between the improvement of diagnostic level of participating physicians and educational background ( Rho=0.07), professional title ( Rho=0.13), age ( r=0.20), and working time of ophthalmofundus disease specialty ( r=0.26). Conclusions:Relying on the three-level online telemedicine training, it can improve the ability of ophthalmologists in Xinjiang region to diagnose fundus diseases. The preliminary telemedicine education model has demonstrated potential for feasibility and effectiveness in remote areas with inadequate medical resources.

Objective:To summarize the clinical phenotype and genetic characteristics of a case of autosomal dominant mental retardation-42 (MRD42) caused by GNB1 gene mutation. Methods:The clinical and genetic data of a case of MRD42 caused by a GNB1 gene missense mutation diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2023 were retrospectively analyzed. The child was followed-up, the child′s data were summarized, and related literature was reviewed. Results:The patient is a 6-month-old female infant, who was admitted to hospital because of "developmental delay for 3 months, intermittent convulsions for 1 month". The clinical manifestations included generalized tonic-clonic seizures, focal seizures, intellectual disability, delayed language and motor development. Long-term video electroencephalogram showed slightly slower background activity, bilateral occipital spike and wave discharges, multispike and wave complexes during sleep. Three focal onset seizures were captured. Cranial magnetic resonance imaging suggested that the subarachnoid space of the bilateral frontotemporal areas was slightly wide. Chromosome karyotype and copy number variation analysis showed no abnormality. The results of whole exon sequencing showed a de novo heterozygous missense mutation in the GNB1 gene [NM_002074:c.155(exon5)G>A;p.Arg52Gln], which had not been reported. The seizure was effectively controlled by function rehabilitation training and anti-epileptic drug therapy. Conclusions:MRD42 is a rare autosomal dominant disorder caused by mutation in the GNB1 gene. The clinical manifestations include infantile-onset seizures, mental retardation, speech and motor development delay, etc. The de novo heterozygous missense mutation in the GNB1 gene c.155G>A(p.Arg52Gln) is the genetic cause of the proband.

Objective:To explore the feasibility and effect of remote medical education model using online film reading training to improve the ability of ophthalmologists in the Xinjiang Uygur Autonomous Region (hereinafter referred to as "Xinjiang Region" ) in diagnosing fundus diseases.Methods:The three-level film reading training system of Xinjiang Production and Construction Corps system division hospital-Corps Hospital-Peking Union Medical College Hospital was established. From June 2022 to January 2023, 4 159 posterior color fundus images were continuously collected from Department of Ophthalmology of Xinjiang Corps Hospital and 4 divisional hospitals in the Corps medical system. Among them, hypertensive retinopathy, diabetic retinopathy, exudative age-related macular degeneration (AMD), atrophic AMD and retinal vein occlusion were 3 073, 651, 43, 186 and 206 cases, respectively. The images were divided into 3 rounds (first, second and last) according to the proportion of diseases. The doctors who participated in the training (hereinafter referred to as the "training") were 15 ophthalmologists from the Corps Hospital of Xinjiang Region and the division hospital of the Corps system. There were 7 male and 8 female. Age was (38.1±4.0) years. The titles of senior, deputy senior, intermediate and junior are 1, 6, 5 and 3 respectively; Bachelor's degree and master's degree are 13 and 2 respectively. The working time of fundus disease specialty was (9.6±3.3) years. The film reading system training was conducted before the first round of labeling, and after each round of film reading, the doctors of Peking Union Medical College Hospital gave feedback and explanation on the film reading results. The diagnostic consistency, sensitivity and specificity were compared by paired sample t test. Spearman or Pearson correlation analysis was conducted between the improvement of diagnostic level and professional title, education, age and working hours of ocular fundus disease. Results:All the participating doctors completed the first, second and last reading. After each round of film reading, the film reading summary was carried out for 2 hours. The average diagnostic agreement rates of participating physicians were 53.0%, 67.0% and 75.0%, respectively. The sensitivity and specificity were 0.38, 0.69, 054 and 0.66, 0.85, 0.96, respectively. There was significant difference between the first and last examination ( P<0.001). The sensitivity of the second reading was significantly higher than that of the first reading, and the sensitivity of the last reading was significantly lower than that of the second reading, with statistical significance ( P<0.05). The specificity of the second reading was significantly higher than that of the first reading, and the last reading was significantly higher than that of the second reading, with statistical significance ( P<0.05). There was no significant correlation ( P>0.05) between the improvement of diagnostic level of participating physicians and educational background ( Rho=0.07), professional title ( Rho=0.13), age ( r=0.20), and working time of ophthalmofundus disease specialty ( r=0.26). Conclusions:Relying on the three-level online telemedicine training, it can improve the ability of ophthalmologists in Xinjiang region to diagnose fundus diseases. The preliminary telemedicine education model has demonstrated potential for feasibility and effectiveness in remote areas with inadequate medical resources.

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Objective:To investigate the perioperative alterations and management of coagulation function in patients of massive blood transfusion during retroperitoneal tumor (RT)resection.Methods:Fourty-seven RT patients at Peking University International Hospital from Jan 2016 to Dec 2021 undergoing resection with massive blood transfusion more than 20 U within 24 h were reviewed for coagulation function before and after surgery.Results:Intraoperative bleeding was 3 000-25 800 ml, 10 patients had blood loss ≥10 000 ml. During the operation, (25.3±9.9) U of red blood cells were transfused, (2 720±1 369) ml plasma transfused, and (2.4±3.3) U platelets were transfused in 6 patients. Fourty-five patients received intraoperative albumin of (79.5±46.5) g; All 47 patients received fibrinogen of (2.3±1.3) g; Prothrombin complex was given in 45 patients (1 205±807) U. Preoperative hemoglobin was statistically different compared to postoperatively and days 1, 3 and 5 ( W=1 790, P<0.001; W=1 672, P<0.001; W=1 704, P<0.001; W=1 486, P=0.004);As with platelets, the difference was also statistically significant compared to postoperative days 1, 3, and 5 ( W=2 153, P<0.001; W=2 092, P<0.001; W=1 732, P<0.001); Preoperative albumin was different compared to postoperative days 1 and 3 ( W=1 568, P<0.001; W=1 578, P<0.001,); Preoperative fibrinogen was different compared to postoperative day 1 ( W=1 964, P<0.001). PT and APTT were prolonged on postoperative days 1 and 3 ( W=628, P<0.001, W=804, P=0.023) ( W=661, P<0.001, W=796, P=0.02). Patient's preoperative fibrin degradation products and D-dimer were above the normal value and were higher on postoperative days 3 and 5 ( W=498, P<0.001, W=345, P<0.001). Conclusions:Coagulation disorders occur perioperatively in patients with massive transfusion while undergoing surgery for RT.The implementation of ratiional transfusion strategy and close postoperative survey and management of coagulation dysfunction help avoid the coagulation related morbidities.

Objective To investigate the effect of plateau hypoxia on the blood-brain barrier after subarachnoid hemorrhage (SAH) in rats. Methods Adult male SD rats (n = 78) were randomly divided into 4 groups: sham group (sham), SAH model group (SAH), plateau hypoxia sham group (Hp sham) and plateau hypoxia SAH model group (Hp SAH). The rat model of plateau hypoxia was established through low-pressure simulation chamber (altitude 5000 m), and the SAH model was established by endovascular perforation method. At 24 hours after SAH, neurobehavior score and SAH grade were assessed. The morphological changes of neurons and apoptosis of nerve cells in the CA1 region of hippocampal were observed by the staining of Nissl and TUNEL. The expression of phosphorylated PI3K (p-PI3K), PI3K, phosphorylated Akt (p-Akt), Akt, phosphorylated nuclear factor κB (p-NF-κB), NF-κB, matrix metalloproteinase-9 (MMP-9), occludin and claudin-5 in hippocampal were detected by the method of Western blotting. The expression of occludin and claudin-5 proteins in the CA1 region of hippocampal were observed by immunofluorescent staining. Results At 24 hours after SAH, the neurobehavior score decreased significantly and SAH grade increased significantly in the SAH and Hp SAH group (P< 0.05). Neurobehavior score decreased significantly in the Hp SAH group compared with the SAH group (P < 0.05). In the SAH group, neurons in the CA1 region of hippocampus were atrophied and deformed, the arrangement were disordered, the number of neurons decreased significantly, and the apoptosis of nerve cells increased significantly(P< 0.05). Plateau hypoxia could aggravate the morphological damage of neurons and apoptosis of nerve cells. The expression of p-PI3K/PI3K, p-Akt/Akt, occludin and claudin-5 proteins decreased significantly, while the expression of p-NF-κB/NF-κB and MMP-9 proteins increased significantly in the SAH and Hp SAH group (P< 0.05). The expression of p-PI3K/PI3K and MMP-9 proteins increased significantly in Hp SAH group compared with the SAH group. The expression of claudin-5 protein increased significantly in Hp sham group compared with the sham group (P < 0.05). Immunofluorescent staining showed that the expression of occludin and claudin-5 proteins in the CA1 region of hippocampus decreased in the SAH group. Plateau hypoxia could further decreased the expression of occludin and claudin-5 proteins. Conclusion Plateau hypoxia aggravates blood-brain barrier disruption after subarachnoid hemorrhage in rats through inhibiting PI3K/Akt/NF-κB pathway.

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).
Child ; Humans ; Hepatitis B Vaccines ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B Antibodies ; Vaccination