Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS). Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of 151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cfPWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling. Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2 rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a 19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Objective:To investigate the risk factors for severe distal curve progression after posterior hemivertebra (HV) resection and short-segment fixation in patients with congenital cervicothoracic scoliosis (CTS), and to analyze the surgical revision strategy.Methods:Imaging and clinical data of patients who underwent posterior HV resection and short-segment fixation for CTS between August 2012 and August 2021 at Nanjing Drum Tower Hospital were retrospectively analyzed. A total of 55 patients were recruited, including 27 females and 28 males with an average age of 8.5±3.6 years (range 3-15 years) at surgery and an average Risser grade of 0.7±1.4 (range 0-4). The number of fused segments averaged 6.9±1.6 (range 4-10), and the mean follow-up was 38.7±18.9 months (range 9-94 months). According to the severity of distal curve progression, the recruited patients were divided into three groups: non-progression group (NPG), mild progression group (MPG), and severe progression group (SPG). The latter two groups were collectively called the progression group (PG). The cervicothoracic Cobb angle, T1 tilt angle, coronal balance distance (CBD), neck tilt angle, clavicular angle, head tilt angle, head shift, and upper (UIV) and lower instrument vertebra (LIV) tilt angle on the standing whole spine X-ray were measured before and after surgery and at the last follow-up. The correction rate of the Cobb angle in the osteotomy area was measured and calculated on CT three-dimensional reconstruction, and the proportion of patients with Klippel-Feil syndrome (KFS) was recorded. Statistical analysis was conducted on the various parameters between the two groups. For factors with statistical significance in the single-factor analysis, binary logistic regression analysis was performed to identify the high-risk factors for distal curve progression.Results:There were 38 cases in the NPG, 11 in the MPG, and 6 in the SPG. Compared to the NPG, the PG showed more severe coronal imbalance preoperatively, with CBD of 35.6±22.3 mm and 11.6±7.1 mm respectively; more severe neck tilt and head shift, with neck tilt angle of 17.4°±8.3° and 12.4°±6.9° respectively, and head shift of 22.8±17.7 mm and 13.9±9.8 mm respectively; and a higher proportion of KFS, 65% (11/17) and 34% (13/38) respectively, all with statistical significance ( P<0.05). Postoperatively, the PG showed more severe coronal imbalance compared with the NPG, with 17.3±12.7 mm and 9.6±8.1 mm respectively; more evident residual deformity, with cervical tilt angles of 9.4°±4.6° and 6.4°±5.3° respectively, and head shift of 14.7±7.4 mm and 9.1±5.9 mm respectively; lower correction of Cobb angle in the apical osteotomy region, with rates of 40.1%±15.2% and 50.3%±19.9% respectively; more significant UIV and LIV tilt, with UIV tilt angles of 14.3°±7.4° and 9.8°±5.3° respectively, and LIV tilt angles of 8.1°±5.5° and 4.5°±3.6° respectively, all with statistical significance ( P<0.05). SPG showed only more severe coronal imbalance preoperatively compared with the MPG, with 50.7±31.3 mm and 27.3±9.6 mm respectively; and head shift, with 33.5±25.0 mm and 16.9±11.0 mm respectively, all with statistical significance ( P<0.05). Logistic regression analysis demonstrated a significant correlation between significant preoperative coronal imbalance and postoperative distal scoliosis progression [ OR=1.299, 95% CI (1.101, 1.531), P=0.002]. Five cases (83.3%) in SPG underwent revision surgery with an average follow-up of 25 months, and selecting the LIV down to the stable region was the major revision strategy. Conclusion:Combined KFS, residual cervicothoracic deformities, and tilting of UIV and LIV are key causes, whereas significant preoperative coronal imbalance is an independent risk factor predisposing to the distal curve progression.

Objective:To compare the clinical outcomes between three-column osteotomy and posterior-column osteotomy for correcting dystrophic kyphoscoliosis secondary to neurofibromatosis type 1 (DKS-NF1).Methods:ALL of 84 patients with DKS-NF1 were retrospectively analyzed, and the average age was 17.7±6.9 years. There were 50 cases with single curve, 18 cases with double curves, and 16 cases with triple curves; kyphosis was found in 42 cases in the thoracic area, 31 cases in the thoracolumbar area, and 11 cases in the lumbar area. The patients were divided into two groups: posterior column osteotomy group and three column osteotomy group based on surgical strategy. The radiographic parameters (including the magnitude of kyphosis, scoliosis, coronal balance distance, etc.) were compared between the two groups before and after surgery, and during the follow-up. The surgical efficacy was also compared based on the spinal correction and complications (such as cerebrospinal fluid leakage, pneumothorax, rod breakage, etc.).Results:The posterior column osteotomy group consisted of 74 patients and the column osteotomy group consisted of 10 patients. The age of patients in the posterior column osteotomy group was significantly younger than that in the three-column osteotomy group (15.8±4.8 years vs. 29.4±10.2 years, t=7.088, P<0.001), and the proportion of preoperative traction in this group was significantly higher than that in the three column osteotomy group (26/74 vs. 0, P=0.027). The apex of kyphosis in the three-column osteotomy group mainly located in the thoracolumbar and lumbar area, significantly higher than that in the posterior column osteotomy group (10/10 vs. 32/74, P=0.001). The magnitude of kyphosis in the two groups were 73.8°±20.9° and 63.1°±21.4° before surgery, respectively ( t=1.506, P=0.136). After surgery, they were corrected to 43.1°±20.9° and 21.1°±22.8°, respectively ( t=3.066, P=0.003), with correction rates of 43.7% ±19.6% and 84.1% ±78.7%, respectively ( t=3.677, P<0.001). At the last follow-up, they were maintained at 46.5°±20.9° and 24.6°±25.5°, respectively ( t=3.016, P=0.003). The Cobb angle of the main curve was corrected from preoperative 83.0°±29.0° and 66.3°±17.7° ( t=1.766, P=0.081) to postoperative 50.6°±20.8° and 40.8°±15.6° ( t=1.436, P=0.155), with correction rates of 38.3% ±16.6% and 39.3% ±12.7% ( t=0.191, P=0.849), respectively. At the last follow-up, they were maintained at 52.3°±20.5° and 43.1°±18.2°, respectively ( t=1.339, P=0.185). The proportion of multi-rod system application and screw density in three column osteotomy group was significantly higher than that in posterior column osteotomy group (8/10 vs. 20/74, P=0.002; 72.0% ±11.3% vs. 61.4% ±14.6%, t=2.173, P=0.033). The incidence of complications in the two groups was 12.2% (posterior column osteotomy group, 9/74) and 20% (three column osteotomy group, 2/10), respectively, with no statistically significant difference ( P=0.613). Conclusion:Three-column osteotomy is mainly used to treat adult kyphosis in DKS-NF1 patients. While the posterior column osteotomy methods were mainly applied in young patients. Most patients can achieve the purpose of deformity correction by posterior column osteotomy alone or combined with anterior complementary fusion. For patients with severe kyphosis, preoperative Halo gravity traction can help to further correct the intraoperative deformities.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Objective:To evaluate whether pelvic fixation is needed in patients undergoing posterior lumbosacral hemivertebra (LSHV) resection and long fusion.Methods:All 32 adult spinal deformity patients with posterior hemivertebra (HV) resection and long segment fixation treated from April 2005 to August 2019 were analyzed retrospectively, including 12 males and 20 females with a mean age of 32.9±8.8 years. According to the state of coronal balance distance (CBD), there were 15 cases of type A (preoperative CBD≤ 30 mm), 1 case of type B (preoperative CBD>30 mm and C 7 plumb line offset to the concave side), and 16 cases of type C (preoperative CBD>30 mm and C 7 plumb line offset to the convex side). The clinical and imaging data before operation, immediately after operation and at the last follow-up were collected, and the short-term and long-term complications related to operation were recorded. The improvement of Cobb angle and coronal balance of primary curve and compensatory curve were evaluated on the whole spine frontal and lateral X-ray films, and the change of coronal balance type after operation was evaluated. According to the mode of distal internal fixation, the patients were divided into two groups: PF group (pelvic fixation): distal fixation to iliac or sacroiliac; NPF group (non-pelvic fixation): distal fixation to L 5 or S 1. Results:All 32 patients were followed up with an average time of 3.9±2.6 years (range 2-11 years). The Cobb angle of primary curve in PF and NPF groups were 42.6°±13.5° and 41.3°±10.9° respectively before operation, and corrected to 13.1°±5.4° and 17.7°±5.8° respectively after operation. It maintained at 13.4°±5.1°and 18.5°±6.7° in the two groups at the last follow-up, respectively ( FPF=32.58, FNPF=28.64, P<0.001). The correction rates were 69.3%±11.8% and 57.6%±10.3%, respectively ( t=2.14, P=0.012). The compensatory curves of in the two groups were corrected from 54.9°±14.8° and 46.8°±13.6° before operation to 17.3°±9.6° and 15.4°±8.4° after operation. It also maintained at 18.5°±8.8°and 17.6°±9.5° in the two groups at the last follow-up, respectively ( FPF=42.97, FNPF=38.56, P<0.001). The correction rates were 68.4%±16.7% and 67.2%±14.9%, respectively ( t=0.17, P=0.849) in the two groups. In PF group, the primary and compensatory curve were similar (69.3%±11.8% vs. 68.4%±16.7%, t=0.15, P=0.837), while the correction rate of compensatory curve in NPF group was significantly higher than that of the primary curve (67.2%±14.9% vs. 57.6%±10.3%, t=2.13, P=0.013). Coronal decompensation occurred in 12 patients (12/32, 37.5%). The CBD in PF and NPF groups was corrected from 33.3±11.2 mm and 28.8±8.1 mm preoperatively to 18.5±3.5 mm and 27.1±6.8 mm postoperatively, respectively, and it showed no significant change at the last follow-up ( FPF=41.61, P<0.001; FNPF=0.38, P=0.896). While the CBD in PF group was significantly better than that in NPF group ( t=3.23, P=0.002; t=2.94, P=0.008). The incidence of coronal decompensation in PF group was 0%, which was significantly lower than 50% (12/24) in NPF group (χ 2=6.40, P=0.014). In addition, 6 cases in PF group were type C coronal decompensation before operation, and the coronal balance was corrected to type A after surgery (100%). Among 10 patients with type C coronal decompensation in NFP, 4 (40%) patients returned to type A after operation, and the difference was statistically significant (6/6 vs. 4/10, χ 2=5.76, P=0.034). Conclusion:Coronal decompensation (12/32, 37.5%) is not rare in patients after posterior LSHV resection and long fusion. Attention should be paid to the match of the corrections between lumbosacral deformity and compensatory curve, which is of great significance in coronal balance reconstruction. Pelvic fixation is helpful to reduce the incidence of postoperative coronal decompensation, especially for the type C patients.

Objective: To investigate the effects of high risk factors questionnaire (HRFQ), Asia-Pacific colorectal screening (APCS) score and their combinations with fecal immunochemical test (FIT) in screening advanced colorectal neoplasia, in order to provide an evidence for further optimization of cancer screening program. Methods: A retrospective cohort study method was used to summarize and analyze the results of colorectal tumor screening in Jiashan County, Zhejiang Province from March 2017 to July 2018. Those with severe diseases that were not suitable for colonoscopy and those with mental and behavioral abnormalities who can not cooperate with the screening were excluded. Those who met any one or more of the followings in the HRFQ questionnaire were classified as high-risk people of HRFQ: (1) first-degree relatives with a history of colorectal cancer; (2) subjects with a history of cancer or any other malignant tumor; (3) subjects with a history of intestinal polyps; (4) those with two or more of the followings: chronic constipation (constipation lasted for more than 2 months per year in the past two years), chronic diarrhea (diarrhea lasted for more than 3 months in the past two years, and the duration of each episode was more than one week), mucus and bloody stools, history of adverse life events (occurring within the past 20 years and causing greater trauma or distress to the subject after the event), history of chronic appendicitis or appendectomy, history of chronic biliary disease or cholecystectomy. In this study, those who were assessed as high risk by HRFQ were recorded as "HRFQ (+)", and those who were not at high risk were recorded as "HRFQ (-)". The APCS questionnaire provided risk scores based on 4 risk factors including age, gender, family history and smoking: (1) age: 2 points for 50-69 years old, 3 points for 70 years old and above; (2) gender: 1 point for male, 0 point for women; (3) family history: 2 points for first-degree relatives suffering from colorectal cancer; (4) smoking: 1 point for current or past smoking, 0 point for non-smokers. The population was divided into low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-7 points). Those who were assessed as high risk by APCS were recorded as "APCS (+)", and those with intermediate and low risk were recorded as "APCS (-)". The hemoglobin threshold for a positive FIT was set to 100 μg/L. Those who were assessed as high risk by APCS with positive FIT were recorded as "APCS+FIT (+)". Those who were assessed as high risk by APCS with negative FIT, those who were assessed by APCS as low-middle risk with positive FIT, and those who were assessed by APCS as low-middle with negative FIT were all recorded as "APCS+FIT(-)". Observation indicators in this study were as follows: (1) the screening compliance rate of the cohort and the detection of advanced colorectal tumors; (2) positive predictive value, negative predictive value, sensitivity and specificity of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors; (3) comparison of the detection rate between HRFQ and APCS questionnaire for different colorectal lesions. Using SPSS 21.0 software, the receiver operating characteristic (ROC) curve was drawn to evaluate the clinical value of HRFQ and APCS combined with FIT in screening advanced colorectal tumors. Results: From 2017 to 2018 in Jiashan County, a total of 53 268 target subjects were screened, and 42 093 people actually completed the questionnaire, with a compliance rate of 79.02%. A total of 8145 cases underwent colonoscopy. A total of 3607 cases among HRFQ positive population (5320 cases) underwent colonoscopy, and the colonoscopy compliance rate was 67. 80%; 8 cases were diagnosed with colorectal cancer and 88 cases were advanced colorectal adenoma. A total of 2977 cases among APCS positive population (11 942 cases) underwent colonoscopy, and the colonoscopy compliance rate was 24.93%; 17 cases were diagnosed with colorectal cancer and 148 cases were advanced colorectal adenoma. The positive rate of HRFQ screening was lower than that of APCS [12.6% (5320/42 093) vs. 28.4% (11 942/42 093), χ²=3195. 547, P<0.001]. In the FIT positive population (6223 cases), a total of 4894 cases underwent colonoscopy, and the colonoscopy compliance rate was 78.64%; 34 cases were diagnosed with colorectal cancer and 224 cases were advanced adenoma. The positive predictive values of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors were 2.67%, 5.54%, 5.44%, and 8.56%; negative predictive values were 94.89%, 96.85%, 96.11% and 96.99%; sensitivity was 29.27%, 50.30%, 12.20 % and 39.02%; specificity was 55.09%, 64.03%, 91.11% and 82.51%, respectively. The ROC curves constructed by HRFQ, APCS, FIT, HRFQ+FIT and APCS+FIT indicated that APCS+FIT presented the highest efficacy in screening advanced colorectal tumors (AUC: 0.608, 95%CI: 0.574-0.642). The comparison of the detection rates of different colorectal lesions between HRFQ and APCS questionnaires showed that there were no significant differences in detection rate of inflammatory polyps and hyperplastic polyps between the two questionnaires (both P>0.05). However, as compared to HRFQ questionnaire, APCS questionnaire had higher detection rates in non-advanced adenomas [26.10% (777/2977) vs. 19.43% (701/3607), χ²=51.228, P<0.001], advanced adenoma [4.97% (148/2977) vs. 2.44% (88/3607), χ²=30.249, P<0.001] and colorectal cancer [0.57% (17 /2977) vs. 0.22% (8/3607), χ²=5.259, P=0.022]. Conclusions: APCS has a higher detection rate of advanced colorectal tumors than HRFQ. APCS combined with FIT can further improve the effectiveness of advanced colorectal tumor screening.
Adenoma/diagnosis* ; Aged ; Asia ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Constipation ; Diarrhea ; Early Detection of Cancer/methods* ; Feces ; Female ; Humans ; Male ; Mass Screening/methods* ; Middle Aged ; Retrospective Studies ; Risk Factors ; Surveys and Questionnaires

OBJECTIVE: To explore the clinical value and safety of unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion by muscle-splitting approach treatment of recurrent lumbar disc herniation. METHODS: The clinical data of 51 patients with recurrent lumbar disc herniation treated from June 2012 to December 2017 were retrospectively analyzed. There were 32 males and 19 females, aged 34 to 64 years with an average of (51.11± 7.28) years. Lesions invoved L RESULTS: There was no statistical difference in operation time between two groups ( CONCLUSION Muscle-splitting approach is feasible for thetreatment of recurrent lumbar disc herniation with pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion. Compared with the median incision approach, the muscle-splitting approach has the advantages of small incision, less trauma, less bleeding, rapid recovery. Also it can protect multifidus and do not increase the incidence of serious complications. Thus, it can be used as a choice for fixation and fusion of recurrent lumbar disc herniation.
Adult ; Female ; Humans ; Intervertebral Disc Degeneration ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Male ; Middle Aged ; Muscles ; Pedicle Screws ; Retrospective Studies ; Spinal Fusion ; Treatment Outcome

Objective:To explore the relationship between breastfeeding knowledge， self-efficacy and exclusive breastfeeding behavior among mothers of one-month old babies. Methods:Random sampling method was conducted for choosing 5 out of 13 community service health centers in Jiading district of Shanghai. A cross-sectional online survey was conducted among the mothers. Results:A total of 456 valid questionnaires were received， the full score of breastfeeding knowledge was set at 60， with an average of 47.17±5.65， ranging from 12 to 60. The full score of self-efficacy was set at 70， with an average of 47.70±14.48， ranging from 14 to 70. The exclusive breastfeeding rate of one-month old infants was 55.3%（252/456）. Multivariate logistic analysis showed that mothers with higher scores of breastfeeding knowledge had significantly higher rate of exclusive breastfeeding （OR=1.717， 95%CI 1.034-2.851， P=0.037）. Those with higher scores of breastfeeding self-efficacy also had significantly higher rate of exclusive breastfeeding （OR=5.736， 95%CI 3.455-9.522， P=0.001）. Conclusions:The breastfeeding knowledge and self-efficacy of mothers of one-month old babies were significantly associated with the rate of exclusive breastfeeding. Medical staff should strengthen the delivery and cultivation of breastfeeding knowledge and skills for mothers to improve breastfeeding self-efficacy， and ultimately promote the rate of exclusive breastfeeding.