OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

BACKGROUND:Percutaneous curved vertebroplasty has the advantages of minimal trauma and bone cement dispersion,but whether it is safe and effective for the treatment of compression fractures in the upper 1/3 of the vertebral body needs further study.OBJECTIVE:To investigate the clinical efficacy of percutaneous curved vertebroplasty in the treatment of the upper 1/3 compression fractures of the osteoporotic vertebrae.METHODS:Medical records of 66 patients with osteoporotic thoracolumbar upper 1/3 compression fracture admitted to Department of Orthopedics of PLA Rocket Force Characteristic Medical Center from January 2020 to June 2023 were retrospectively analyzed.Among them,32 cases were treated with percutaneous curved vertebroplasty(observation group)and 34 cases were treated with"noncoplanar bipedicular puncture"percutaneous vertebroplasty(control group).Pain visual analog scale score,Oswestry Disability Index,anterior edge height of injured vertebra,and Cobb angle of injured vertebra were compared and analyzed between the two groups before surgery,the first day after surgery,and the last follow-up.The operative time,bone cement leakage rate,bone cement injection volume,and bone cement dispersion score of the two groups were statistically analyzed.RESULTS AND CONCLUSION:(1)The operations were successfully completed in both groups of patients,and no complications such as bone cement allergy,bone cement embolism,nerve damage,or epidural hematoma occurred.(2)Pain visual analog scale score,Oswestry disability index,anterior edge height,and Cobb angle of injured vertebra of the two groups at the first day after surgery and the last follow-up were all better than those before surgery,with statistically significant difference(P＜0.05),but there was no statistical significance between the two groups(P＞0.05).The Oswestry disability index of the two groups at the last follow-up was better than that on the first day after surgery(P＜0.05).(3)The operation time and bone cement leakage rate of the observation group were lower than those of the control group,and the differences were statistically significant(P＜0.05).(4)There were no significant differences in bone cement injection volume and bone cement dispersion score between the two groups(P＞0.05).(5)The results show that percutaneous curved vertebroplasty in the treatment of osteoporotic vertebrae compression fractures in the upper 1/3 of the vertebral body can effectively relieve pain,maintain vertebral height,and reduce operative time and bone cement leakage rate.

Objective To analyze the occurrence and risk factors of needlestick and sharps injuries(NSIs)among oral health care workers(HCWs).Methods NSIs reported by West China Hospital of Stomatology from 2020 to 2023 were collected,and factors relevant to NSIs were analyzed.Results A total of 391 cases of NSIs were repor-ted.Only one case of injury was caused by a sterile device,while the remaining 390 cases were caused by contamina-ted devices.There were 85,107,113,and 86 cases in 2020,2021,2022,and 2023,respectively.Most NSIs oc-curred among interns(n=235,60.1％).294 cases(75.2％)of NSIs occurred among HCWs who had less than 3 years of clinical experience.The distribution of NSIs among 235 interns in different months showed that NSIs ac-counted for a relatively high proportion from April to June and July to September,and the difference was statistica-lly significant(P＜0.05).The ventral side of the left thumb was the most common site of NSIs(n=53,13.6％),followed by the ventral side of the right index finger(n=45,11.5％)and the ventral side of the left index finger(n=44,11.3％).The most common devices involved in NSIs were various types of syringe needles(n=84,21.5％),followed by various types of dental burs(n=76,19.4％)and suture needles(n=49,12.5％).Injuries mainly oc-curred during the treatment process(n=212,54.2％)and in the department of endodontics(n=86,22.0％).This study didn't find any occupational bloodborne infection case caused by NSIs.Conclusion NSIs mainly occur among inexperienced oral interns,and devices causing NSIs are related to the treatment process.

Objective:To analyze the selection of internal fixation methods, surgical outcomes, and complications in patients with Neurofibromatosis Type 1 (NF1) accompanied by dystrophic lumbosacral deformities, and to evaluate the indications for pelvic fixation.Methods:A retrospective analysis was conducted on 21 patients with NF1 and associated dystrophic lumbosacral malformations (L 4 to sacrum) who underwent spinal deformity correction surgery at Nanjing Drum Tower Hospital from January 2009 to November 2022. The cohort included 11 males and 10 females, with a mean surgical age of 15.4±4.7 years (range, 7-24 years). Patients were divided into two groups based on whether pelvic fixation was performed: 10 patients in the non-pelvic fixation group (NP group) and 11 in the pelvic fixation group (P group), where fixation involved second sacral alar-iliac (S 2AI) screws or iliac screws. Radiographic parameters, including the Cobb angle of the lumbosacral fractional curve, main curve, and focal kyphosis, were compared preoperatively, postoperatively, and at the last follow-up. Results:The NP group had a significantly lower mean age (13.2±4.9 years) compared to the P group (17.5±3.5 years; t=2.287, P=0.034). Spinal instability (rotational subluxation or spondylolisthesis) due to dystrophic changes was observed in 2 patients in the NP group and 8 in the P group, a statistically significant difference (χ 2=5.838, P=0.030). In the P group, five patients underwent unilateral fixation and six underwent bilateral fixation. Implant types included 2 cases with iliac screws, 1 case with iliac screws plus S 2AI, and 8 cases with S 2AI screws alone. The utilization rate of hooks was significantly higher in the NP group (12.6%±11.5%) compared to the P group (3.5%±6.9%; t=2.230, P=0.038). The preoperative Cobb angle of the lumbosacral fractional curve was significantly smaller in the NP group (13.8°±9.0°) than in the P group (25.5°±13.9°; t=2.228, P=0.039). Postoperatively, the angles were corrected to 6.3°±6.1° and 6.4°±5.3°, respectively ( t=0.901, P=0.969), with correction rates of 57.3%±13.6% and 74.1%±17.8% ( t=2.369, P=0.029). At final follow-up, the angles remained stable (6.6°±6.6° vs. 6.3°±4.8°; t=0.116, P=0.909). For the main curve, preoperative Cobb angles were 52.5°±15.1° (NP) and 61.1°±16.9° (P; t=1.200, P=0.246), corrected to 31.3°±13.8° and 28.0°±8.4°, respectively ( t=0.646, P=0.526). Correction rates were 41.3%±13.0% in the NP group and 53.2%±11.6% in the P group ( t=2.206, P=0.037). At the final follow-up, these values were 32.4°±14.2° and 31.7°±10.3° ( t=0.133, P=0.896). Focal kyphosis, seen in 9 patients, was corrected from 19.7°±10.9° preoperatively to -13.6°±9.5° postoperatively, and remained at -14.1°±9.6° at the final follow-up ( F=33.547, P<0.001). Multi-rod systems were used in 6 cases (NP group) and 7 cases (P group), with no significant difference (χ 2=0.153, P=0.926). Two patients in the NP group developed coronal decompensation three years postoperatively, and one required revision surgery. In the P group, rod breakage occurred in 3 patients, two of whom underwent revision. Conclusions:Dystrophic rotational subluxation or spondylolisthesis of the lumbosacral spine is a primary indication for pelvic fixation in patients with NF1-associated deformities. However, complications related to internal fixation remain common. The combined use of a multi-rod screw-hook hybrid system, particularly when extending across the lumbosacral region, may reduce the risk of instrumentation failure.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective:To investigate the clinical characteristics of encephalocraniocutaneous lipomatosis (ECCL) in pediatric patients.Methods:A retrospective analysis was conducted on the clinical data of 2 ECCL cases admitted to Children′s Hospital Affiliated to Zhengzhou University between January 2024 and December 2024. Additionally, a review of relevant literature was performed to summarize the clinical features of this condition.Results:Case 1 is a male patient aged 2 years and 10 months, while case 2 is a female patient aged 8 months. Both patients presented with seizures and exhibited nevus psiloliparus on the scalp, non-scarring alopecia, nodular skin tags around the eyes, and ocular choristomas. Brain magnetic resonance imaging revealed leptomeningeal angiomatosis in both cases, with case 1 also demonstrating an intracranial lipoma and case 2 showing localized cerebral atrophy and an arachnoid cyst. Whole-exome sequencing of peripheral blood and copy number variation analysis in both cases did not identify any pathogenic variants. Additionally, no relevant pathogenic variants were detected in the scalp lesion tissue of case 2. A review of the literature revealed that, to date, there have been 5 reported domestic cases, 132 reported foreign cases in pediatric populations, totally 139 cases including 2 cases described in this article. Among these patients, 86 are male, 49 are female, and the gender of 4 cases remains unspecified. Clinical manifestations observed included seizures in 79.0% (64/81) of cases and developmental delay in 64.7% (57/88). Cutaneous lesions were characterized by non-scarring alopecia in 100% (97/97) of cases,non-hair-bearing fatty tissue nevi in 98.3% (58/59), nodular skin tags in 96.5% (56/58), and subcutaneous lipomas in 94.8% (73/77). Ocular lesions predominantly involved choristomas, occurring in 91.8% (90/98) of cases. Central nervous system abnormalities were identified as ventricular dilatation or hydrocephalus in 85.0% (68/80) of cases, intracranial lipomas in 82.1% (69/84), localized cerebral atrophy in 80.9% (34/42), intracranial vascular anomalies in 74.1% (23/31), and spinal lipomas in 66.6% (30/45).Conclusions:ECCL is an uncommon neurocutaneous disorder with the potential to impact various organ systems, notably the integumentary, ocular, and central nervous systems. Pediatric patients may exhibit symptoms such as seizures, developmental delays, and additional clinical manifestations, necessitating vigilant monitoring and management.

OBJECTIVE To explore the distribution and drug resistance of the pathogens causing the abdominal(pelvic)soft tissue infections in secondary or above medical institutions of Suzhou so as to provide bases for pre-vention and control of the infections.METHODS The surveillance data of abdominal(pelvic)soft tissue infections that were reported regularly from 58 member institutions of Suzhou from Jan.2020 to Dec.2023 were collected from the regional nosocomial infection surveillance platform by Suzhou nosocomial infection management and qual-ity control center.Totally 26 tertiary hospitals and 32 secondary hospitals were involved.RESULTS Most of the 1178 strains of pathogens were isolated from the tertiary hospitals,the proportion of gram-negative bacteria was the highest;Escherichia coli,Klebsiella pneumoniae and Enterococcus faecium ranked the top 3 species.The constituent ratio of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains the was highest among the mul-tidrug-resistant organisms.The K.pneumoniae and CRKP strains were sensitive to tigecycline;the E.coli strains were highly sensitive to carbapenems,minocycline and piperacillin-tazobactam;Stenotrophomonas maltophilia strains were highly resistant to most of the antibiotics;Enterobacter cloacae strains were highly resistant to ampi-cillin-sulbactam but were highly sensitive to carbapenems;the drug resistance rate of the A.baumannii strains to tigecycline was less than 5％;the drug resistance rate of Pseudomonas aeruginosa strains to ticarcillin-clavulanic acid was highest.CONCLUSIONS The abdominal(pelvic)soft tissue infection is always mixed infections.The pathogens show severe drug resistance.It is necessary to strengthen the surveillance of etiological spectrum and drug resistance and conduct targeted guidance for clinical practice of diagnosis and treatment.

Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.

Objective:To investigate the efficacy of cementless long-stem total hip arthroplasty (THA) in the treatment of end-stage osteonecrosis of the femoral head (ONFH) combined with ipsilateral subtrochanteric femoral fractures.Methods:A retrospective case series study was conducted on 18 patients with end-stage ONFH combined with ipsilateral subtrochanteric fractures who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from January 2016 to June 2023, including 8 males (8 hips) and 10 females (10 hips), aged 56-79 years [(69.4±7.0)years]. All the patients had Association Research Circulation Osseous (ARCO) stage IV ONFH combined with ipsilateral subtrochanteric fracture (Seinsheimer types II-IV). Parameters recorded included operation duration, intraoperative blood loss, length of hospital stay, time to partial weight-bearing, and time to full weight-bearing. Vertical offset and leg length discrepancy (LLD) were compared preoperatively and at 1 week postoperatively. Visual analogue scale (VAS) score, hip range of motion (flexion, abduction), and Harris hip score (HHS) were compared preoperatively, at 1 week, 3 months postoperatively, and at the last follow-up. Perioperative complications were observed.Results:All the patients were followed up for 12-70 months [(36.4±16.2)months]. Operation duration was (116.4±18.1)minutes. Intraoperative blood loss was (334.4±121.3)ml. The length of hospital stay was 13.0(10.0, 16.3)days. The time to partial weight-bearing was 5.0(3.0, 7.0)days, with time to full weight-bearing for 5.0(4.0, 5.3)weeks. At 1 week postoperatively, the vertical offset [(58.9±4.1)mm] was significantly increased compared to that preoperatively [(49.3±3.3)mm] ( P<0.01), while the LLD [(4.2±3.1)mm] was significantly reduced compared to that preoperatively [(16.2±5.8)mm] ( P<0.01). At 1 week, 3 months postoperatively and at the last follow-up, the VAS scores [3.0(2.0, 3.3)points, 2.0(1.0, 2.0)points, and 1.0(0.0, 2.0)points] were significantly lower than that preoperatively [6.0(5.0, 6.3)points], and decreased with the passage of follow-up time ( P<0.01); the hip flexion angles [(50.4±6.5)°, (94.3±6.4)°, and (104.7±7.4)°] and hip abduction angles [(21.5±4.4)°, (34.9±4.5)°, and (42.9±4.9)°] were lower than those preoperatively [(32.9±6.4)° and (13.4±4.9)°], and decreased with the passage of follow-up time ( P<0.01); the HHS [(58.1±4.9)points, (83.1±2.9)points, and (90.7±2.6)points] were higher than that preoperatively [(33.4±4.4)points], and increased with the passage of follow-up time ( P<0.01). At the last follow-up, 5 patients were rated as excellent, 11 as good, and 2 as fair according to the HHS criteria, with an overall excellent and good rate of 89%. No perioperative complications were observed, including neurovascular injury, secondary fracture, or infection. One patient developed partial deep vein thrombosis of the lower extremity (the popliteal vein) at 2 weeks after surgery, which recovered completely following treatment with a standard oral administration of rivaroxaban, etc. At the last follow-up, no evidence of malunion, prosthesis loosening, subsidence, or dislocation was observed. Conclusion:The use of cementless long-stem THA in the treatment of end-stage ONFH combined with ipsilateral subtrochanteric fractures has advantages of small trauma, early weight-bearing, early pain relief, improved joint motion and function, and few complications.

Objective:To investigate the surgical outcomes of congenital cervicothoracic scoliosis (CTS) patients with Klippel-Feil syndrome (KFS) and prognostic characteristics across different subtypes.Methods:A retrospective case series study is conducted. Clinical and radiographic data of 41 CTS patients with KFS who underwent hemivertebra resection with instrumentation at Department of Orthopedic Surgery, Nanjing Drum Tower Hospital from March 2012 to September 2022, with a minimum follow-up of two years, were analyzed. The cohort included 16 males and 25 females, aged (8.6±3.7) years (range: 3 to 15 years). Preoperative, immediate postoperative, and final follow-up cervicothoracic deformity parameters were compared. Patients were classified into three subtypes based on preoperative coronal alignment: shoulder-neck type (type A, 16 cases), trunk-tilt type (type B, 16 cases), and thoracic compensatory curve type (type C, 9 cases). The severity of KFS and the incidence of distal curve progression among subtypes were analyzed. Repeated measurement data were compared by repeated measurement ANOVA, pairwise comparison within groups was performed by Bonferroni method, and categorical variables were compared by Chi-square test or Fisher exact probability method.Results:All patients underwent successful surgery. Twenty-one patients (53.7%) had cervical fusion of ≥3 segments, and 63.1% (82/130) of fused cervical segments were located proximally to the instrumentation. Postoperative cervicothoracic Cobb angle, head tilt, head shift, neck tilt, and clavicle angle significantly improved (all P<0.05). The proportion of patients with cervical fusion of ≥3 segments was higher in types B and C (17/25) than that in type A (5/16) ( χ2=5.299, P=0.021). Four type B (4/16) and 5 type C (5/9) patients underwent long-segment fixation, with stable coronal alignment postoperatively. The remaining patients received short-segment fixation. In the short-segment group, the incidence of distal curve progression was significantly higher in types B and C (8/16) than that in type A (1/16) ( P=0.015). Ultimately, 3 type B patients underwent revision surgery, and 1 type C patient met the criteria for revision (distal compensatory thoracic or lumbar curve>40°). Conclusions:CTS patients with KFS are predisposed to develop significant coronal malalignment involving trunk tilt (type B) or thoracic compensatory curve (type C) before surgery. Following hemivertebra resection with short-segment fixation, such patients have a high risk of distal curve progression and potential need for revision surgery.