ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Objective:To measure and analyze upper lip morphology variation before and after the cross-arch fixed restoration of the maxillary implant-supported prostheses using cone- beam CT (CBCT) to provide an esthetic objective reference for maxillary edentulous patients.Methods:There were 32 maxillary edentulous patients selected in the Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University from January 2010 to December 2023. The CBCT data of patients with maxillary full-arch implant-supported fixed prostheses were retrospectively collected before implantation (T0), at the time of radio-guide insertion (T1), and after final repair (T2). The length and thickness of the upper lip were measured and analyzed at each time point, and the correlation between the upper lip contour data and facial esthetic parameters was analyzed.Results:After the final prosthodontic treatment, the length of the upper lip was significantly increased from (21.72±2.84) mm to (24.98±2.93) mm ( t=-8.13, P<0.001) compared with that before implant treatment. The widths of the middle and vermilion of the upper lip (Sm-Hm/Ls-UP), were reduced from (13.24±1.41), (12.81±1.67) mm to (11.36±1.67), (10.21±1.69) mm, with significant differences ( t=7.79, P<0001; t=9.37, P<0.001). The lower face height (Sn-Gn) was increased from (54.52±4.95) mm to (58.70±4.42) mm, with significant differences ( t=-11.05, P<0.001). However, the nasolabial angle reduced significantly from 95.35°± 7.70°to 90.53°±7.28°( t=7.68, P<0.001). The width of the middle of the upper lip with a radiation guide was (10.94±1.24) mm, and it increased significantly compared with that after the final prosthesis treatment ( t=-0.76, P<0.05). The proportion of straight upper lip profiles accounted for 59% (19/32), and the proportion of concave upper lip profiles accounted for 41% (13/32) after the final prosthesis treatment. In addition, the results of correlation analysis showed that the nasolabial angle variation was weak and negatively correlated with residual bone height ( r=-0.37, P=0.490). Conclusions:After the treatment of the maxillary full-arch implant-supported fixed prosthesis, the length of the upper lip increases, and the thickness of the upper lip becomes significantly thin. The maxillary full-arch implant-supported fixed prostheses support upper lips to improve the patients′ side appearances.

Objective To explore the application value of static progressive stretch(SPS)combined with step-wise progressive rehabilitation nursing in perioperative rehabilitation nursing of patients with unicompartmental knee arthroplasty(UKA).Methods From January 2022 to June 2023,a total of 74 patients who were scheduled to undergo UKA in the Department of Orthopedics of a tertiary A hospital in Beijing were selected by the convenient sampling method and divided into 2 groups by the random number table method,with 37 cases in each group.The experimental group was given step-by-step rehabilitation nursing combined with SPS technology,while the control group was only given step-by-step rehabilitation nursing,and the intervention lasted for 4 weeks.The knee joint activity,knee joint function score,comfort,and rehabilitation self-efficacy of the 2 groups were observed and measured before and after the intervention.Results Finally,35 patients were included in the experimental group and 36 patients in the control group.After the intervention,the knee joint range of motion,knee joint function score,comfort,rehabilitation self-efficacy and all dimensions and their total scores in the experimental group were higher than those before the intervention and those in the control group(P＜0.05).Conclusion SPS combined with progressive rehabilitation nursing can effectively improve the knee joint function and range of motion of patients after UKA,improve the comfort of patients,improve their quality of life,and enhance their rehabilitation self-efficacy,which is helpful to achieve early recovery.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

Objective:To explore effect of rubusoside(RS) on myocardial injury in gestational diabetes mellitus(GDM) rats and its mechanism.Methods:Pregnant SD rats were divided into control, GDM model, insulin treatment(INS), RS, endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA), and RS+ endoplasmic reticulum stress inducer thapsigargin(THA) groups. Glycolipid metabolism, cardiac function, serum LDH, cTnI, and CK-MB levels, myocardial tissue morphology, SOD, GSH, MDA, Fe 2+ content were assessed. ROS levels were assessed using DHE staining, and iron ion deposition was evaluated via Prussian blue staining. The expression of endoplasmic reticulum stress and ferroptosis related proteins in myocardial tissue after intervention was analyzed through Western blot and immunohistochemistry. Results:Compared with control rats, GDM model rats showed increased body weight, FBG, TC, TG, abnormal cardiac function, significant myocardial damage, elevated serum LDH, cTnI, CK-MB, reduced SOD and GSH, increased MDA, Fe 2+, ROS, and iron ions, along with altered protein expression indicating endoplasmic reticulum stress and ferroptosis. RS and 4-PBA mitigated these changes, reducing myocardial injury. THA reversed RS′s protective effects via the endoplasmic reticulum stress-ferroptosis pathway. Conclusion:RS improves glycolipid metabolism and alleviates myocardial injury in GDM rats by inhibiting endoplasmic reticulum stress and reducing ferroptosis.

OBJECTIVE: To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type II C (GA II C). METHODS: Clinical data of a 32-year-old pregnant woman and her fetus with GA II C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq). RESULTS: At 18 weeks' gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks' gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c.1285+1G＞A and c.343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PS3_Supporting; PVS1+PM2_Supporting+PM3). CONCLUSION The c.1285+1G＞A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus. Type II C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.
Pregnancy ; Humans ; Female ; Mutation ; DNA Copy Number Variations ; Oligohydramnios/genetics* ; Retrospective Studies ; Phenotype ; Fetus/diagnostic imaging*

OBJECTIVE: To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia. METHODS: The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed. RESULTS: The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo. CONCLUSION For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.
Female ; Humans ; Pregnancy ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit ; DNA Copy Number Variations ; Growth Disorders ; Retrospective Studies

OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.
Male ; Female ; Humans ; Child ; Albuterol/therapeutic use* ; Prospective Studies ; Muscular Atrophy, Spinal/drug therapy* ; Spinal Muscular Atrophies of Childhood/drug therapy* ; Treatment Outcome

Objective:To analyze the characteristics of lung function in patients with spinal muscular atrophy (SMA) to provide evidence for multidisciplinary management of SMA.Methods:A total of 30 patients with SMA treated in the SMA multidisciplinary clinic of the Children′s Hospital, Zhejiang University School of Medicine from July 2019 to March 2021 were enrolled, including 1 child with type I, 18 patients with type Ⅱ and 11 children with type Ⅲ.There were 17 males and 13 females; the age ranged from 4 years to 21 years and 10 months old.A retrospective study was conducted to analyze the clinical features, spinal imaging findings and lung functions of patients with different clinical types of SMA and explore the factors influencing the lung functions of patients with SMA.Pulmonary function was measured by forced expiratory flow-volume curve.Forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC and peak expiratory flow (PEF) were measured.The results were expressed as the percentage of the measured value to predicted value.The Cobb angle was measured to evaluate scoliosis. Pearson correlation analysis and multiple linear regression analysis were used to evaluate the relationship between lung function and age and Cobb angle in patients with type Ⅱ SMA. Pearson correlation analysis and univariate linear regression analysis were used to evaluate the relationship between Cobb angle and age in patients with type Ⅱ SMA. Results:Pulmonary function in 1 type I patient showed decreased FVC and FEV 1; Among 18 patients with type Ⅱ, 14 cases had abnormal lung function (77.8%): FVC decreased in 12 patients (66.7%), FEV 1 decreased in 10 patients (55.6%), PEF decreased in 12 patients (66.7%). Among 11 patients with type Ⅲ, one had decreased FVC (9.1%). FVC, FEV 1 and PEF of patients with type Ⅱ were significantly lower than those of patients with type Ⅲ [(62.4±31.8)% vs.(90.8±11.0)%, (66.3±33.3)% vs.(97.8±9.9)%, (65.3±30.1)% vs.(98.6±21.1)%, all P<0.01]. Pearson correlation analysis showed that FVC of patients with type Ⅱ SMA was correlated with age and Cobb angle ( r=-0.864, -0.865, all P<0.001), FEV 1 was correlated with age and Cobb angle ( r=-0.878, -0.863, all P<0.001), PEF was correlated with age and Cobb angle ( r=-0.831, -0.783, all P<0.001), and Cobb angle was related to age ( r=0.922, P<0.001). Multiple linear regression analysis indicated that FVC of patients with type Ⅱ SMA was linearly correlated with Cobb angle ( R2=0.748, P<0.001), FEV 1 was linearly correlated with age ( R2=0.770, P<0.001), PEF was linearly related to age ( R2=0.690, P<0.001). Univariate linear regression analysis revealed that Cobb angle of patients with type Ⅱ SMA was linearly related to age ( R2=0.851, P<0.001). Conclusions:FVC, FEV 1 and PEF may decrease in patients with SMA.The degree of lung function damage is different in different types of SMA patients.With the increase of age, Cobb angle increases and FVC, FEV 1 and PEF decrease in patients with type Ⅱ SMA.Understanding the factors influencing the pulmonary function damage in patients with SMA is conductive to carrying out individual multidisciplinary management.

The clinical data of a case with late-onset isolated sulfite oxidase deficiency(ISOD)admitted in the Department of Neurology, Children′s Hospital, Zhejiang University School of Medicine in July 2021 were retrospectively analyzed.Fifteen previously published cases of late-onset ISOD were also reviewed.The patient was a girl, who was hospitalized because of " motor regression with mental retardation for 5 days" at 1 year old.The manifestations of the patient were extrapyramidal symptoms, regression of motor development and seizures.The level of urinary sulfites in the patient was increased.Magnetic resonance imaging (MRI) features were bilateral pallidus and substantia nigra.Gene sequencing suggested a pure missense mutation of the sulfite oxidase( SUOX) gene c. 650(exon5)G>A(p.Arg217Gln). In 16 cases of late-onset ISOD, the median age at onset and diagnosis was 10.5 months and 34.0 months, respectively.The common clinical manifestations were hypotonia (13 cases), seizures (10 cases), movement disorders (9 cases), and ectopia lentis (6 cases). The most common brain MRI feature was pallidus changes (11 cases), followed by lesions of substantia nigra (5 cases), and cerebral atrophy (4 cases). Fourteen cases of late-onset ISOD showed a positive urinary sulfite test.The missense mutation of the SUOX gene was found in 9 cases.It suggested that brain MRI involvement of bilateral pallidus, high excretion of urine sulfites and the missense mutation of the SUOX gene were important diagnostic clues for late-onset ISOD.