1.Huangqin Decoction alleviates ulcerative colitis in mice by reducing endoplasmic reticulum stress
Jianguo QIU ; Yitong QIU ; Guorong LI ; Linsheng ZHANG ; Xue ZHENG ; Yongjiang YAO ; Xidan WANG ; Haiyang HUANG ; Fengmin ZHANG ; Jiyan SU ; Xuebao ZHENG ; Xiaoqi HUANG
Journal of Southern Medical University 2024;44(11):2172-2183
Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.
2.Huangqin Decoction alleviates ulcerative colitis in mice by reducing endoplasmic reticulum stress
Jianguo QIU ; Yitong QIU ; Guorong LI ; Linsheng ZHANG ; Xue ZHENG ; Yongjiang YAO ; Xidan WANG ; Haiyang HUANG ; Fengmin ZHANG ; Jiyan SU ; Xuebao ZHENG ; Xiaoqi HUANG
Journal of Southern Medical University 2024;44(11):2172-2183
Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.
3.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.
4.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.
5.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.