1.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
2.Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation
Zhen RUAN ; Shenghua HE ; Xuehua GONG ; Song QIAO ; Chao WANG
China Pharmacy 2024;35(9):1087-1093
OBJECTIVE To study the improvement effect and mechanism of sanguinarine (SG) on inflammatory pain in rats with lumbar disc herniation (LDH) and its mechanism. METHODS LDH model rats were established and divided into model group, SG low-dose, medium-dose and high-dose groups (1.00, 2.50, 6.25 mg/kg), high-dose of SG+Anisomycin [mitogen-activated protein kinase (MAPK) activator] group (6.25 mg/kg SG+5 mg/kg Anisomycin), with 10 rats in each group. Another 10 rats were included as the control group. Each group was given corresponding drugs intraperitoneally, while the control group and model group were given an equal volume of normal saline intraperitoneally, once a day, for 7 consecutive days. The general situation and neurological changes of rats in each group were observed, and the pain threshold [including paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL)] of rats was determined; the histopathological changes of dorsal root ganglion (DRG) were observed in rats. The serum levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)] and pain factors [neuropeptide Y (NPY), 5-hydroxytryptamine (5-HT)] in rats were detected.The positive expressions of ionized-calcium binding adaptor molecule-1 (Iba-1) in spinal cord microglia and glial fibrillary acidic protein (GFAP) in astrocytes were observed. The expressions of proteins related to MAPK/extracellular signal-regulated kinase (ERK)/nuclear factor κB (NF-κB) signaling pathway, TNF-α and IL-1β proteins were detected in DRG tissue of rats. RESULTS Compared with the control group, the rats in the model group showed decreased appetite, hindlimb movement disorders, and disordered neuronal cell arrangement, the neurological score, the levels of TNF-α, IL-1β, NPY, the positive expressions of Iba-1 and GFAP, the phosphorylations of p38 MAPK, ERK1/2 and NF-κB p65, the protein expressions of TNF-α and IL-1β were significantly increased (P<0.05); PWMT, PWTL and the levels of 5-HT were significantly reduced (P<0.05). Compared with the model group, the rats of SG groups showed some relief in their mental appetite and hindlimb motor disorders, the intervertebral disc structure of DRG was restored, and the levels of the above quantitative indicators had significantly reversed (P<0.05). Anisomycin reversed the improvement effect of SG on inflammatory pain in LDH rats. CONCLUSIONS SG can improve inflammatory pain by inhibiting the activation of microglia in DRG tissue of LDH rats, reducing the release of inflammatory factors, and increasing pain threshold, and its mechanism of action may be related to the inhibition of MAPK/ERK/NF- κB signaling pathway.
3.Severe distal curve progression and its revision strategy following posterior osteotomy and fusion for congenital cervicothoracic scoliosis
Saihu MAO ; Kai SUN ; Song LI ; Jie ZHOU ; Yitong ZHU ; Zhen LIU ; Benlong SHI ; Xu SUN ; Jun QIAO ; Bin WANG ; Yang YU ; Yong QIU ; Zezhang ZHU
Chinese Journal of Orthopaedics 2024;44(8):509-518
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.
4.Comparison of surgical outcomes between three-column osteotomy and posterior column osteotomy for correcting type I neurofibromatosis associated with kyphoscoliosis
Song LI ; Zezhang ZHU ; Jie ZHOU ; Saihu MAO ; Yitong ZHU ; Zhen LIU ; Benlong SHI ; Xu SUN ; Jun QIAO ; Bin WANG ; Yang YU ; Yong QIU
Chinese Journal of Orthopaedics 2024;44(8):569-577
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.
5.Comparison of the Nerve Regeneration Capacity and Characteristics between Sciatic Nerve Crush and Transection Injury Models in Rats.
Bin Bin WANG ; Chao GUO ; Sheng Qiao SUN ; Xing Nan ZHANG ; Zhen LI ; Wei Jie LI ; De Zhi LI ; Michael SCHUMACHER ; Song LIU
Biomedical and Environmental Sciences 2023;36(2):160-173
OBJECTIVE:
To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them.
METHODS:
Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury.
RESULTS:
Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups.
CONCLUSION
The regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.
Animals
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Rats
;
Nerve Fibers
;
Nerve Regeneration
;
Rats, Sprague-Dawley
;
Sciatic Nerve/injuries*
6.Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway.
Miao YANG ; Wen-Jing YU ; Chun-Xiang HE ; Yi-Jie JIN ; Ze LI ; Ping LI ; Si-Si DENG ; Ya-Qiao YI ; Shao-Wu CHENG ; Zhen-Yan SONG
China Journal of Chinese Materia Medica 2023;48(2):534-541
This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.
Rats
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Animals
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Mitophagy
;
Alzheimer Disease/genetics*
;
Powders
;
Protein Kinases/metabolism*
;
Ubiquitin-Protein Ligases/metabolism*
7.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
8.Pelvic fixation for posterior lumbosacral hemivertebra resection and long fusion in adult spinal deformity
Song LI ; Zezhang ZHU ; Saihu MAO ; Yanyu MA ; Yitong ZHU ; Zhen LIU ; Benlong SHI ; Xu SUN ; Jun QIAO ; Bin WANG ; Yang YU ; Yong QIU
Chinese Journal of Orthopaedics 2022;42(7):426-436
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.
9.Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Yi ZHANG ; Yan QIAO ; Li LI ; Dan-Dan GAO ; Jing-Yan SONG ; Zhen-Gao SUN
Chinese journal of integrative medicine 2022;28(8):675-682
OBJECTIVE:
To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age.
METHODS:
This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed.
RESULTS:
Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results.
CONCLUSIONS
QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).
Drugs, Chinese Herbal/therapeutic use*
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Embryo Transfer
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Female
;
Fertilization in Vitro
;
Gonadotropin-Releasing Hormone/agonists*
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Humans
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Ovulation Induction
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Pregnancy
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Pregnancy Outcome
;
Pregnancy Rate
10.Mid-term outcomes of one-stage posterior-only jumping hemivertebra resections and short fusions for children with congenital scoliosis secondary to multiple hemivertebrae
Saihu MAO ; Song LI ; Zezhang ZHU ; Yanyu MA ; Zhen LIU ; Benlong SHI ; Xu SUN ; Jun QIAO ; Bin WANG ; Yang YU ; Yong QIU
Chinese Journal of Orthopaedics 2021;41(23):1673-1682
Objective:To evaluate the safety and efficacy of one-stage posterior-only jumping hemivertebra (HV) resection combined with respective short fusions in the treatment of congenital scoliosis (CS) caused by multiple HVs.Methods:All of 13 consecutive patients with multiple HVs treated surgically from January 2010 to December 2017 were retrospectively reviewed, including 4 males and 9 females with a mean age of 3.7±1.2 years. One child had 4 HVs, and the rest had 2 HVs. The responsible HVs causing local scoliosis/kyphosis deformity or coronal plane deviation were selected as the target of resection. The distal HV was removed firstly and then the proximal one was resected; both of the fixation vertebraes were horizontalized during surgery. The clinical and imaging data of the children before the initial operation, immediately after the operation and at the latest follow-up were collected, and the short-term and long-term complications related to surgery were recorded. The data were evaluated on the whole-standing spine anteroposterior and lateral films, including the corrections of proximal and distal main curves, coronal balance, local kyphosis, and the improvement of spinal growth height (upper and lower internal fixation length, T 1-S 1 length). At the same time, the re-progression of coronal and sagittal deformities of the spine during growth was recorded (coronal decompensation: emerging postoperative curve progression more than 20°; kyphosis progression: kyphosis aggravation between upper and lower internal fixation more than 40°) and internal-fixation-related complications (screw cutting, screw malposition) were recorded. Results:Dual HVs were resected in each child, of which 8 (61.5%) were located on contralateral side of the spine, and 5 (38.5%) were located on ipsilateral side of the spine. The follow-up time was 6.2±3.3 years (range 2.0-10.5 years) after surgery. The Cobb angles of proximal and distal main curves were 36.7°±11.8° and 35.2°±7.8° respectively before surgery and were corrected to 9.7°±6.6° and 6.1°±4.1° respectively after surgery ( F=31.249, F=93.83, P< 0.001) ( t=6.888, t=10.954, P<0.001), and the correction rates was 73.6%±19.6% and 82.7%±11.7%, respectively. They were maintained at 14.3°±5.4° and 8.0°±4.6° at the latest follow-up, showing the correction rates loss of 15.8%±26.9% and 6.9%±7%, respectively. The coronal balance improved from 17.2±14.8 mm pre-operatively to -0.2±15.7 mm postoperatively ( t=2.703, P=0.008), and it remained at 0±18.4 mm at the final follow-up ( F=4.137, P=0.024). The T 1-S 1 length was corrected to 273.8±27.3 mm postoperatively, slightly increased compared with pre-operation 256.3±24.0 mm, ( t=0.680, P=0.527), and significantly increased to 333.2±33.4 mm at the latest follow-up ( t=2.986, P<0.001; F=6.704, P=0.003). Seven patients had local kyphosis before operation, which was significantly improved from 32.2°±13.6° to 6.1°±9.8° with a correction rate of 93.4%±27.0% after surgery ( t=3.355, P=0.004), which showed no significant loss of correction at the latest follow-up (5.4°±10.4°) ( F=11.187, P=0.002). Six patients (46.2%) developed coronal decompensation (Curve magnitude >20 °), with an average of 21.7°±1.9°. Two cases (15.4%) had progressive kyphosis between the thoracic regional internal fixations at 3 months after surgery, which were 68° and 58° respectively. After bracing, both coronal decompensation and sagittal kyphosis were improved. At the last follow-up, the coronal decompensation was improved to 14.7±8.9° and the kyphosis was alleviated to 55° and 46°, respectively. Conclusion:Posterior-only skipping hemivertebra resection and short fusion is a safe, effective procedure yielding significantly improvement of the growth imbalance and reginal spinal deformities of CS with multiple HVs. The mid-term follow-up results showed that the progress of the scoliosis was common during the growth period, which could be further controlled by supplementary brace treatment.

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