Objective:To investigate the clinical efficacy of botulinum toxin type A（BTX-A）bladder injection in the treatment of neurogenic detrusor overactivity（NDO）with autonomic dysreflexia（AD）.Methods:The patients with spinal cord injury at or above T6，who were treated at Guangdong Provincial Work Injury Rehabilitation Hospital from January 2018 to December 2022，were included in this study prospectively. Inclusion criteria：①chronic spinal cord injury patients over 18 years old（with no progression of neurological symptoms within 3 months）；② presence of NDO and AD；③ inadequate response or intolerance to oral antimuscarinic agent（M-receptor antagonists or β 3-receptor agonists）④ perform clean intermittent catheterization to empty the bladder. Exclusion criteria：① primary disease in the acute or progressive phase；② previous surgeries that would affect lower urinary tract function，such as transurethral sphincterotomy，bladder neck resection，prostatectomy，or bladder surgery；③ allergy to BTX-A or its adjuvants，or those with allergic predisposition ④ patients who were pregnant，breastfeeding，or planning for pregnancy in the near future；⑤ patients did not accept or were unable to perform intermittent catheterization. Before treatment，all patients were required to maintain 3-5 day urine diary，along with urodynamic studies（UDS），incontinence specific quality of life instrument（I-QOL）and AD symptom severity assessment，and blood pressure monitored. Key UDS parameters recorded included maximum bladder capacity，maximum detrusor pressure during filling phase，changes in maximum systolic blood pressure（SBP）relative to baseline（ΔSBP）during UDS examination，and the frequency of 24-hour blood pressure exceeding baseline by 20 mmHg. After general anesthesia or epidural anesthesia，BTX-A（200 U）was injected into the bladder at 30 points（including the triangle）under the cystoscope using a special injection needle，6.7 U per injection，and then the catheter was kept for 3-5 days after treatment. Three months later，relevant indicators were collected and compared with pre-treatment data. Results:A total of 43 patients were included in this study，including 34 males and 9 females. The age was（39.23±13.17）years old and the disease course was（2.69±3.27）years old. There were 33 cervical and 10 thoracic cases. The American Spinal Injury Association Injury Scale score distribution was as follows：26（60%）A，4（9%）B，9（21%）C，and 4（9%）D. The presence of AD was confirmed in all patients during urodynamic examination（UDS），that was the systolic blood pressure（SBP）suddenly increased and exceeded 20 mmHg（1 mmHg = 0.133 kPa）. Before treatment，The AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（14.53±2.51），Bladder-related AD frequency was 10.67 episodes/day. Baseline SBP was（103.51±9.64）mmHg，the maximum SBP was（150.40±22.75）mmHg，and the change in SBP（ΔSBP）from maximum to baseline SBP during UDS examination was（43.83±21.01）mmHg. The UDS indicated that the maximum detrusor pressure during storage phase was（54.95±24.68）cmH 2O，and the bladder capacity was（131.70±75.29）ml. Bladder diary showed the volume of catheterization each time from was（181.16±49.86）ml，and The I-QOL score was（44.07±8.60）. Three months after treatment，the AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（11.37±2.39）. The frequency of bladder-related AD episodes was（7.51±2.37）episodes/day，showing statistically significant differences compared to pre-treatment（ P<0.05）.The SBP before UDS examination was（102.12±10.28）mmHg，with no statistically significant difference from baseline（ P = 0.518）. The maximum SBP in perfusion phase and the ΔSBP were（132.84±16.30）mmHg and（28.72 ± 14.02）mmHg，respectively，both demonstrating statistically significant differences（ P < 0.05）. The UDS examination revealed that the maximum detrusor pressure during the storage phase was（29.77±13.72）cmH 2O，showed a significant decrease，and the bladder capacity was（272.63±79.75）ml，which were both statistically different before and after surgery. Bladder diary showed the volume of catheterization each time was（326.74±63.71）ml；I-QOL score was（71.86±11.45），both were significant different after treatment（ P < 0.01）. Conclusion:BTX-A intravesical injection in the treatment of NDO can also alleviate the severity and frequency of bladder related AD.

Objective:To investigate the clinical efficacy of botulinum toxin type A（BTX-A）bladder injection in the treatment of neurogenic detrusor overactivity（NDO）with autonomic dysreflexia（AD）.Methods:The patients with spinal cord injury at or above T6，who were treated at Guangdong Provincial Work Injury Rehabilitation Hospital from January 2018 to December 2022，were included in this study prospectively. Inclusion criteria：①chronic spinal cord injury patients over 18 years old（with no progression of neurological symptoms within 3 months）；② presence of NDO and AD；③ inadequate response or intolerance to oral antimuscarinic agent（M-receptor antagonists or β 3-receptor agonists）④ perform clean intermittent catheterization to empty the bladder. Exclusion criteria：① primary disease in the acute or progressive phase；② previous surgeries that would affect lower urinary tract function，such as transurethral sphincterotomy，bladder neck resection，prostatectomy，or bladder surgery；③ allergy to BTX-A or its adjuvants，or those with allergic predisposition ④ patients who were pregnant，breastfeeding，or planning for pregnancy in the near future；⑤ patients did not accept or were unable to perform intermittent catheterization. Before treatment，all patients were required to maintain 3-5 day urine diary，along with urodynamic studies（UDS），incontinence specific quality of life instrument（I-QOL）and AD symptom severity assessment，and blood pressure monitored. Key UDS parameters recorded included maximum bladder capacity，maximum detrusor pressure during filling phase，changes in maximum systolic blood pressure（SBP）relative to baseline（ΔSBP）during UDS examination，and the frequency of 24-hour blood pressure exceeding baseline by 20 mmHg. After general anesthesia or epidural anesthesia，BTX-A（200 U）was injected into the bladder at 30 points（including the triangle）under the cystoscope using a special injection needle，6.7 U per injection，and then the catheter was kept for 3-5 days after treatment. Three months later，relevant indicators were collected and compared with pre-treatment data. Results:A total of 43 patients were included in this study，including 34 males and 9 females. The age was（39.23±13.17）years old and the disease course was（2.69±3.27）years old. There were 33 cervical and 10 thoracic cases. The American Spinal Injury Association Injury Scale score distribution was as follows：26（60%）A，4（9%）B，9（21%）C，and 4（9%）D. The presence of AD was confirmed in all patients during urodynamic examination（UDS），that was the systolic blood pressure（SBP）suddenly increased and exceeded 20 mmHg（1 mmHg = 0.133 kPa）. Before treatment，The AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（14.53±2.51），Bladder-related AD frequency was 10.67 episodes/day. Baseline SBP was（103.51±9.64）mmHg，the maximum SBP was（150.40±22.75）mmHg，and the change in SBP（ΔSBP）from maximum to baseline SBP during UDS examination was（43.83±21.01）mmHg. The UDS indicated that the maximum detrusor pressure during storage phase was（54.95±24.68）cmH 2O，and the bladder capacity was（131.70±75.29）ml. Bladder diary showed the volume of catheterization each time from was（181.16±49.86）ml，and The I-QOL score was（44.07±8.60）. Three months after treatment，the AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（11.37±2.39）. The frequency of bladder-related AD episodes was（7.51±2.37）episodes/day，showing statistically significant differences compared to pre-treatment（ P<0.05）.The SBP before UDS examination was（102.12±10.28）mmHg，with no statistically significant difference from baseline（ P = 0.518）. The maximum SBP in perfusion phase and the ΔSBP were（132.84±16.30）mmHg and（28.72 ± 14.02）mmHg，respectively，both demonstrating statistically significant differences（ P < 0.05）. The UDS examination revealed that the maximum detrusor pressure during the storage phase was（29.77±13.72）cmH 2O，showed a significant decrease，and the bladder capacity was（272.63±79.75）ml，which were both statistically different before and after surgery. Bladder diary showed the volume of catheterization each time was（326.74±63.71）ml；I-QOL score was（71.86±11.45），both were significant different after treatment（ P < 0.01）. Conclusion:BTX-A intravesical injection in the treatment of NDO can also alleviate the severity and frequency of bladder related AD.

Objective:To study the results of thalassemia gene detection and prenatal diagnosis in pregnant women in Ningbo City, and analyze the characteristics of erythrocyte parameters in early pregnancy.Methods:A total of 636 suspected thalassemia pregnant women treated in Ningbo Women and Children's Hospital from January 2019 to September 2021 were selected as the research subjects, the dry blood spots of pregnant women were collected for thalassemia gene detection; and the amniotic fluid of pregnant women with thalassemia gene carried by both husband and wife was extracted for prenatal diagnosis, and the results of thalassemia gene detection and prenatal diagnosis were analyzed. Meanwhile, in the medical record system of Ningbo Women and Children's Hospital, the detection results of erythrocyte parameters in early pregnancy of pregnant women with thalassemia gene (thalassemia group) and healthy pregnant women (control group) were investigated. Erythrocyte parameters including hemoglobin (Hb), red blood cell count (RBC), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin content (MCH), mean corpuscular volume (MCV), hematocrit (HCT) and red blood cell distribution width (RDW) were compared between groups and among different thalassemia gene variants.Results:Among 636 suspected thalassemia pregnant woman, 254 cases (39.94%) were confirmed thalassemia gene carriers, including 114 cases of α-thalassemia, 132 cases of β-thalassemia, and 8 cases of αβ-compound thalassemia. After genetic counseling, 11 women finally received prenatal diagnosis, 7 fetuses (7/11) were found to carry thalassemia gene, including two cases of -- SEA/αα and β CD17/β N, respectively; one case of β CD26/β N, αα/-α 3.7 and β CD41-42/β CD41-42, respectively. The results of erythrocyte parameters detection showed that compared with the control group ( n = 80), there were statistically significant differences ( P < 0.05) in various erythrocyte parameters in α-thalassemia group ( n = 77) and β-thalassemia group ( n = 87); and there were significant differences ( P < 0.05) in Hb, HCT, MCV, MCH and MCHC among the four major genotypes (-- SEA/αα, β IVS-Ⅱ-654/β N, β CD17/β N and β CD41-42/β N). Conclusions:The genetic testing of thalassemia in pregnant women in Ningbo City is mainly α-thalassemia or β-thalassemia, and prenatal diagnosis is necessary for pregnant women carrying thalassemia gene. The erythrocyte parameters in early pregnancy of pregnant women carrying thalassemia gene are changed, and there are differences among different genotypes.

Objective:To study the genotyping of thalassemia in Ningbo population and provide a reference basis for future prevention and control of thalassemia in Ningbo.Methods:Patients with suspected thalassemia attending Ningbo Women and Children's Hospital from January 2019 to March 2022 were selected for the study, and DNA was extracted from dried blood spot specimens by collecting peripheral blood, and detection of thalassemia hotspot variants was performed by fluorescence PCR melting curve analysis combined with Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA).Results:A total of 2 680 cases were included in the patients with suspected thalassemia, and 1 426 cases of thalassemia gene carriers were detected, with an overall detection rate of 53.2%. Among them, 595 cases (41.7%) were α-thalassemia, with -- SEA/αα, αα/-α 3.7 and -- SEA/-α 3.7 being more common; 807 cases (56.6%) were β-thalassemia, with β IVS-Ⅱ-654/β N, β CD41-42/β N and β CD17/β N being more common; 24 cases (1.7%) were αβ-combined thalassemia. Among them, six rare variant types were included, including fusion gene (Fusion), -- FIL, HBA2:c.376C>T, CD8/9(+G), IVS-Ⅰ-2(T>C) and IVS-Ⅱ-1(G>A), all of which were reported for the first time in Ningbo. Conclusion:Among suspected thalassemia patients in Ningbo, the detection rate of thalassemia is high, and the types of gene variants are complex, so the awareness of thalassemia gene testing for anemic patients should be raised.

Objective:To explore the type and composition of thalassemia gene variation in children in Ningbo City, and to analyze its correlation with erythrocyte parameters.Methods:From January 2019 to December 2020, 785 children who underwent thalassemia gene testing in Ningbo Women and Children's Hospital were selected as the retrospective research subjects to analyze the type and composition of thalassemia gene variation in local children. A total of 238 thalassemia gene mutation carriers and 100 healthy children (control group) who underwent physical examination during the same period were selected for routine blood test to analyze the correlation between thalassemia gene mutation types and serological indexes.Results:Among the 785 children who underwent thalassemia gene testing, 571 were confirmed as carriers of thalassemia gene mutation, with a detection rate of 72.7%, including 228 cases of α-thalassemia, 337 cases of β-thalassemia, and 6 cases of αβ-complex type thalassemia. It covered 17 variant types and 25 gene combinations. There were significant differences in red blood cell count (RBC), hematokrit (HCT), hemoglobin concentration (Hb), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell distribution width (RDW) between the control, α-thalassemia and β-thalassemia groups ( H/ F = 125.03, 86.24, 141.06, 192.99, 121.46, 198.63, 178.06, P < 0.001). And there were statistically significant differences in HCT, Hb, MCH, MCV and RDW among the four common genotypes (-- SEA/αα, β IVS-Ⅱ-654/β N, β CD41-42/β N and β CD17/β N) in this test ( F = 5.03, 3.34, 6.24, 10.33, 6.83, P < 0.05). Conclusion:The genotypes of children with thalassemia in Ningbo City are diverse, and the erythrocyte parameters are different among different genotypes.

OBJECTIVE: To explore the clinical phenotype and genetic basis for a fetus suspected for Coffin-Siris syndrome. METHODS: Chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were carried out for the fetus. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound at 23rd gestational week has revealed fetal ventriculomegaly. No abnormality was found by CMA, while WES revealed that the fetus has harbored a de novo heterozygous c.2851G>A (p.G951R) variant of the SMARCA4 gene, which was predicted to be pathogenic. CONCLUSION Genetic testing should be considered for fetuses featuring progressive widening of lateral cerebral ventricles.
Female ; Humans ; Pregnancy ; DNA Helicases/genetics* ; Fetus ; Genetic Testing ; Nuclear Proteins/genetics* ; Phenotype ; Transcription Factors/genetics* ; Exome Sequencing

OBJECTIVE: To explore the clinical features and genomic abnorm ality of a fetus enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation. METHODS: The fetuse was found to have multicystic dysplastic kidneys with oligohydramnios upon ultrasonography during the second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Sanger sequencing was used to verify the suspected variants in the family. RESULTS: Antenatal ultrasound examination at 19 weeks showed "polycystic" kidneys with Oligohydramnios. Delivery was by induced labour because of the critically low amniotic fluid volume. Testing of CMA was normal. WES showed a compound heterozygous mutation of c.1817G>A, p.W606X; c.432dupA, p.E145Rfs*18 mutations are novel mutations in this study. CONCLUSION The research may further expand the NPHP3 gene mutation spectrum. Enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation at least include one or two splice site mutation, frameshift mutation or nonsense mutation foetal poor prognosis.
Amniotic Fluid ; Female ; Humans ; Kidney Diseases, Cystic ; Multicystic Dysplastic Kidney/genetics* ; Mutation ; Oligohydramnios/genetics* ; Polycystic Kidney Diseases ; Pregnancy ; Ultrasonography, Prenatal

OBJECTIVE: To establish a newborn screening system for Duchenne muscular dystrophy (DMD) through assessment of MM isoenzyme of creatine kinase (CK-MM) activity. METHODS: The CK-MM level was detected using dry blood spot filter paper from 10 252 male newborns. The results were grouped based on their gestational age, sampling time and intervals between the experiments. The threshold value for CK-MM necessitating genetic testing was determined. Next-generation sequencing (NGS) was carried out for those with a CK-MM value over the threshold, and the result was verified by multiplex ligation-dependent probe amplification (MLPA). RESULTS: Based on the result of non-parametric rank sum test, the median CK-MM concentration has increased with the gestational age, and was inversely correlated with the age of the newborns among unaffected specimens. CK-MM on dry blood spot filter paper can be stable for 14 days at 2-8℃. Statistical analysis of CK-MM value of the 10 252 neonates suggested that the threshold may be set as 700 ng/mL. Exonic deletions were found in 2 confirmed cases, whose CK-MM level was greater than 2000 ng/mL. CONCLUSION Detection of CK-MM in dry blood spot filter paper has provided an effective method for newborn screening of DMD. This simple and inexpensive method can be used for large-scale screening, which is of great value to the early intervention and treatment of the disease.
Dystrophin/genetics* ; Exons ; Humans ; Infant, Newborn ; Male ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne/genetics* ; Neonatal Screening

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-β₁ （TGF-β₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （P<0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （P<0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （P<0.01）， and scores of three symptom dimensions were lower than those in control group （P<0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （P<0.01）， and CD8⁺ was lower than those in the control group （P<0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-β₁ were lower than those in the control group （P<0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （χ²=4.572， P<0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

Objective:To assess effect of detection of plasma N terminal pro brain natriuretic peptide (NT‐proBNP) and serum cystatin C (Cys C) combined Global Registry of Acute Coronary Events (GRACE) score on heart func‐tion and prognosis in patients with acute coronary syndrome (ACS) .Methods :According to GRACE score ,a total of 136 ACS patients were divided into low risk group (n=29) ,intermediate risk group (n=39) and high risk group (n=68) .Serum Cys C level and plasma NT‐proBNP level were measured in all groups .Incidence rate of major ad‐verse cardiovascular events (MACE) within three and six months was counted .Results:Among ACS patients ,com‐pared with low risk group ,there were significant rise in levels of NT‐proBNP [ (165.80 ± 51.62) ng/L vs .(193.13 ± 74.64) ng/L vs .(985.45 ± 152.69) ng/L] and Cys C [ (0.83 ± 0.38) mg/L vs .(0.9 ± 0.25) mg/L vs .(1.23 ± 0.23) mg/L] ,left ventricular end‐diastolic diameter [six months: (50 ± 3) mm vs .(55 ± 3) mm vs .(59 ± 5) mm] ,significant reduction in left ventricular ejection fraction [LVEF ,six months: (55 ± 7)% vs .(49 ± 5)% vs . (40 ± 7)% ] ,and significant rise in incidence rate of MACE (six months:2.94% vs .9.55% vs .30.88% ) ,and a‐bove indexes in high risk group were significantly higher than those of intermediate risk group except LVEF signifi‐cantly reduced , P<0.05 or <0.01 ;Pearson correlation analysis indicated that NT‐proBNP and Cys C levels were positively correlated with GRACE score (r=0.72 , P<0.05 ; r=0.65 , P<0.05) respectively .Conclusion:NT‐proBNP and Cys C level detection combined GRACE score could exactly response heart function and prognosis .