Background::With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods::We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).Results::There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion::For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Objective:To compare the efficacy of acetabular magic hook plates versus quadrilateral area combined plates in treating complicated acetabular fractures.Methods:A retrospective analysis was conducted on 44 cases of complicated acetabular fractures treated at the Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2017 to August 2022. Among these cases, 21 were treated with magic hook plate internal fixation (hook plate group) and 23 with quadrilateral area combined plate internal fixation (combined plate group). In the hook plate group, there were 15 males and 6 females, with an average age of 43.1±11.8 years. According to the Letournel-Judet classification, there were 13 double-column fractures, 5 anterior column with posterior semi-transverse fractures, and 3 T-type fractures. Additionally, 8 cases were classified as B2.2 type, 5 as C1 type, 4 as C2 type, and 4 as C3 type; 15 cases were APQ1 type and 6 were APQ2 type. In the combined plate group, there were 16 males and 7 females, with an average age of 41.7±12.8 years. This group included 15 double-column fractures, 6 anterior column with posterior semi-transverse fractures, and 2 T-type fractures. Additionally, there were 8 cases of B2.2 type, 6 cases of C1 type, 4 cases of C2 type, and 5 cases of C3 type; 15 cases were APQ1 type and 8 were APQ2 type. Comparative analyses included operative time, intraoperative blood loss, fracture healing time, Matta standard assessment, modified Merle d'Aubign-Postel scores, and postoperative complications.Results:All 44 patients were followed up for 10 to 24 months, with an average follow-up of 14 months. The acetabular fractures healed in all cases. The healing time was 3.6±0.9 months for the hook plate group and 3.7±0.9 months for the combined plate group, with no significant difference between the groups ( t=0.549, P=0.586). The hook plate group had an operative time of 138.3±30.7 minutes and intraoperative blood loss of 735.7±159.8 ml, compared to 163.9±48.7 minutes and 843.5±181.1 ml, respectively, in the combined plate group, both of which were statistically significant ( P<0.05). The reduction quality was excellent in 13 cases, good in 5 cases, and poor in 3 cases in the hook plate group, with an excellent and good rate of 86% (18/21). In the combined plate group, the reduction quality was excellent in 13 cases, good in 6 cases, and poor in 4 cases, with an excellent and good rate of 83% (19/23), showing no significant difference between the groups (χ 2=0.143, P=0.931). The modified Merle d'Aubign Postel scores of the hook plate group were 13.8±2.2 points, 15.3±2.5 points and 16.7±1.8 points at 3 months, 6 months and the last follow-up, respectively, and the combined plate group were 13.1±1.9 points, 14.6±2.1 points and 16.4±2.0 points, respectively ( P>0.05). However, both groups showed statistically significant improvements in hip function over time ( F=9.658, P<0.001; F=16.195, P<0.001). Wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in one case each in both groups. In the combined plate group, there were 3 cases of incision fat liquefaction, 2 cases of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis. No other complications such as incision infection, iliac vascular injury, or loss of internal fixation were observed in either group. Conclusion:Both magic hook plate fixation and quadrilateral area combined plate fixation are safe and effective for treating complex acetabular fractures. However, magic hook plate fixation offers advantages in reducing operative time and intraoperative blood loss, thereby simplifying and enhancing the safety of the procedure.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To investigate the efficacy and safety of the "frame and buttress" fixation in the treatment of acetabular quadrilateral fractures.Methods:A total of 26 patients with acetabular quadrilateral fractures treated with the "Frame and buttress" fixation strategy (reconstructing frame and providing buttress for quadrilateral surface) from January 2017 to January 2021 were retrospectively analyzed in the Department of Orthopaedics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, including 17 males and 9 females, aged 47.7±16.5 years, (range, 25-71 years). There were 13 cases from car accidents, 8 cases from falls, and 5 cases from heavy objects. Quadrilateral fractures were classified according to whether the anterior column (A) and posterior column (P) of the acetabulum were fractured and whether the quadrilateral plate (Q) was partially (1) or completely (2) separated from the two columns. Among these cases, there were 5 cases of type AQ1, 1 case of type AQ2, 1 case of type PQ2, 14 cases of type APQ1 and 5 cases of type APQ2. The "frame and buttress" fixation strategy was used to perform open reduction and internal fixation. The Matta scale was used to assess the quality of resurfacing based on pelvic radiographs, and the Matta modified Merle d'Aubigne and Postel scores were referenced to evaluate hip function.Results:All the 26 patients successfully completed the operation, the operation time was 88.1±57.8 min (range, 90-320 min), the intraoperative bleeding was 753.8±309.5 ml (range, 400-1 400 ml). There were 14 cases of anatomical reduction, 8 cases of satisfactory reduction and 4 cases of unsatisfactory reduction with an excellent rate of 85% (22/26), the excellence rate was 85% (22/26). All patients were followed up for 16.3±4.3 months (range, 12-24 months). The hip function score after operation was higher than that before operation, and the difference was statistically significant ( F=19.80, P<0.001). The hip function score was 13.1±2.2 at 3 months postoperatively, increased to 15.9±2.3 at 6 months postoperatively, and increased to 16.6±1.9 at the last follow-up, with a statistically significant difference ( P<0.001). After operation, 5 patients showed symptoms of lateral femoral cutaneous nerve injury such as hypoesthesia and numbness in the anterolateral thigh. During the follow-up, there was no ectopic ossification, traumatic arthritis, necrosis of the femoral head and central dislocation of the femoral head. Conclusion:The "frame and buttress" fixation strategy based on quadrilateral fracture typing for acetabular quadrilateral fracture open reduction internal fixation provides strong fixation, satisfactory reduction quality, and facilitates joint function recovery after operation.

Objective:To evaluate the efficacy of infra-acetabular screw placement assisted by orthopedic navigation robot in the treatment of acetabular fractures.Methods:The data of 34 patients who were treated and followed up from September 2021 to September 2022 were retrospectively analyzed. According to the fixation method, the patients were divided into the robot group (robot assisted placement of infra-acetabular screws) and the control group (placement of the pubis-ischium plate manually). There were 16 patients in the robot group, 7 males and 9 females, aged 57.00±6.00 years (range, 51-70 years). According to Letournel classification, there were 8 cases of both-column fractures, 4 cases of anterior column and posterior hemitransverse fractures, and 4 cases of T-shaped fractures. There were 18 cases in the control group, 8 males and 10 females, aged 54.22±8.95 years (range, 38-69 years). According to Letournel classification, there were 10 cases of both-column fractures, 6 cases of anterior column and posterior hemitransverse fractures, and 2 cases of T-shaped fractures. The intraoperative fluoroscopy times, total operation time, exposure time and screw placement (plate) time, blood loss, Matta evaluation, Majeed score, and screw placement accuracy rate (the degree of screw cutting-out was evaluated according to Lonstein criteria) were compared between the two groups.Results:All patients were followed up for 12.21±3.62 months (range, 6-17 months). In the robot group, the fluoroscopy frequency was 9.69±0.95 times (range, 8-11 times), the screw placement time was 34.32±5.28 min (range, 21-45 min), and the blood loss was 461.88±228.71 ml (range, 200-800 ml). The control group was 10.11±1.41 times (range, 7-13 times), 42.89±4.38 min (range, 36-55 min), 674.44±220.65 ml (range, 420-1,100 ml), respectively. There were significant differences in screw (plate) placement time ( t=5.18, P<0.001) and blood loss ( t=2.76, P<0.001). The accuracy of robot screw placement was 100%. According to Lonstein evaluation, there were 14 cases of grade 0 (87.5%, 14/16) and 2 cases of grade I (12.5%, 2/16). At 30 days of follow-up, all patients had good fracture ends and no internal fixation failure occurred. One week after surgery, the results of Matta evaluation in robot group were excellent in 11 cases, good in 3 cases, and poor in 2 cases, with an excellent and good rate of 87.5%. In the control group, 11 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 83.3%. There was no significant difference in the excellent and good rate of Matta evaluation between the two groups (χ 2=0.23, P=0.892). At last follow-up, the Majeed score of robot group was 87.81±8.82 (range, 71-98), including excellent in 10 cases, good in 5 cases, and fair in 1 case. The score of the control group was 86.22±6.85 (range, 70-95), including 12 cases of excellent, 4 of good, and 2 of fair. There was no significant difference in Majeed score between the two groups ( t=0.59, P=0.551). No complications related to the use of robot-assisted navigation or plate fixation were observed in both groups. Conclusion:Through the navigation planning and assistance of the robot, the infra-acetabular screws can be accurately and safely placed, which avoids the shortcomings of excessive exposure and bleeding during the application of the pubis-ischium plate, the outcome was similar to that of plate treatment.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

OBJECTIVE:To evaluate the efficacy and safety of cerebrolysin in adjuvant treatmenut of acute cerebral infarction systematically,and to provide evidence-based reference in clinic.METHODS:Retrieved from SCI,Cochrane Library,EMBase,PubMed,CJFD,VIP and Wanfang Database,RCTs about cerebrolysin combined with routine plan (trial group) vs.routine plan alone or combined with placebo (control group) in adjuvant treatment of acute cerebral infarction were collected.After data extraction and quality evaluation by using Cochrane systematic review manual 5.1.0,Meta-analysis was conducted by using Rev Man 5.2 statistical software.RESULTS:A total of 20 RCTs were included,involving 3 313 patients.Meta-analysis showed that NIHSS score [MD=-1.77,95％CI(-2.33,-1.21),P＜0.001],response rate [OR=2.85,95％CI(1.75,4.63),P＜0.001] and Barthel index (BI) score [MD =7.30,95 ％ CI (3.48,11.13),P＜ 0.001] in trial group were significantly higher than control group,with statistical significance.There was no statistical significance in disability rate [OR=0.46,95％ CI(0.20,1.03),P=0.06],mortality [OR=0.79,95％ CI (0.52,1.19),P=0.25],the incidence of ADR [OR=1.04,95％ CI (0.85,1.27),P=0.72] or the incidence of severe ADR [OR=0.01,95％CI(-0.02,0.04),P=0.51] between 2 groups.CONCLUSIONS:Cerebrolysin is good for adjanctive therapy of acute cerebral infarction,can significantly improve neurologic impairment and life quality and dosen't increase the incidence of ADR.

BACKGROUNDGenetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.

METHODSThe study group comprised 639 postmenopausal women aged (62.2 ± 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2 w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment.

RESULTSThe FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 ± 84.1) mg/cm(2)) than those with AC genotypes ((703.0 ± 86.9) mg/cm(2)) and AA genotypes ((649.8 ± 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.

CONCLUSIONSFDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

Alendronate ; therapeutic use ; Asian Continental Ancestry Group ; Bone Density Conservation Agents ; therapeutic use ; Female ; Geranyltranstransferase ; genetics ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; Polymorphism, Genetic

OBJECTIVETo investigate the influence of ozonated water on physical and chemical properties of vacuum sealing drainage (VSD) materials.

METHODSVSD materials (foam and sealing membrane) were immersed in 10 µg/ml ozonated water for 1 h twice daily for 8 days. The foam appearance and microscopic structure of the materials were observed, and tensile tests and Raman spectrum scan were performed assess the effect of ozonated water. Simulated VSD devices were prepared and tested for leakproofness under negative pressure after ozonated water treatment.

RESULTSzonated water treatment for 8 days caused no obvious abnormal changes in the foam appearance or microscopic structure of the materials. The maximum tensile load of foam before and after ozonated water treatment was 4.25∓0.73 kgf and 2.44∓0.19 kgf (P=0.000), the momentary distance when the foam torn before and after intervention was 92.54∓12.83 mm and 64.44∓4.60 mm, respectively (P=0.000). The corresponding results for VSD sealing membrane were 0.70∓0.58 kgf and 0.71∓0.08 kgf (P=0.698), and 99.30∓10.27 mm and 100.95∓18.22 mm (P=0.966), respectively. Raman spectroscopy revealed changes in only several wave intensities and no new chemical groups appeared within the scan range of 400-4000 cm(-1). The VSD device was well hermetic after treatment with ozonated water.

CONCLUSIONExcept for a decreased stretch resistance property of the foam, VSD materials display no obvious changes in physical and chemical characteristics after treatment with ozonated water for 8 days.

Biomedical and Dental Materials ; chemistry ; Drainage ; instrumentation ; methods ; Ozone ; Vacuum ; Water ; chemistry

Objective To explore whether the respective implantation of vascular bundles and sensory nerve tracts into a tissue-engineered bone will affect the expression of CGRP (Calcitonin gene related peptide) and its receptor. Methods Fifty-four New Zealand rabbits were randomly divided into 3 even groups for implantation of sensory nerve tracts (group A),implantation of vascular bundles (group B),and a control group of simple tissue-engineered bone (group C) . Animals were sacrificed 4,8,12 weeks after implantation,respectively. Masson staining was conducted to observe the process of bone formation and re-molding. CGRP and CGRPR-1 expressions in the new bone were measured by immunohistochemistry and Real-time PCR at 4,8 and 12 weeks after implantation. Results At all time points,the CGRP and CGRPR-1 expressions in groups A and B were significantly higher than in group C (P<0.05),and those in group A were higher than in group B too (P<0.05) . Over time,the expressions of CGRP and CGRPR-1 mRNA in each group in the new bone tissue were gradually reduced after an initial increase. The neuropeptide expression at the 8th week was higher than those at the 4th and 12th weeks. The neuropeptide expression at the 4th week was the lowest. The expression of CGRP was mainly localized in the periphery of newly generated bone,periosteum and the blood vessels. The expression of CGRPR-1 was mainly localized in the periphery of osteoblasts. Conclusions Implantation of either vascular bundles or sensory nerve tracts can promote neuropeptide secretion. The vascular bundle implantation may result in higher expressions of CGRP and CGRPR-1 than sensory nerve tract implantation.