Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials.

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No adverse event signals were detected in the treatment groups. Conclusion and Relevance: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.

Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease.

BACKGROUND: The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown. METHODS: In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab. RESULTS: In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).

Integrating genomics and transcriptomics to identify candidate genes for high-altitude adaptation and egg production in Nixi chicken.

1. This study combined genome-wide selection signal analysis with RNA-sequencing to identify candidate genes associated with high altitude adaptation and egg production performance in Nixi chickens (NXC).2. Based on the whole-genome data from 20 NXC (♂:10; ♀:10), the population selection signal was analysed by sliding window analysis. The selected genes were screened by combination with the population differentiation statistic (FST). The sequence diversity statistic (θπ). RNA-seq was performed on the ovarian tissues of NXC (n = 6) and Lohmann laying hens (n = 6) to analyse the differentially expressed genes (DEGs) between the two groups. The functional enrichment analysis of the selected genes and differentially expressed genes was performed.3. There were 742 genes under strong positive selection and 509 differentially expressed genes screened in NXC. Integrated analysis of the genome and transcriptome revealing 26 overlapping genes. The candidate genes for adaptation to a high-altitude environment, as well as for egg production, disease resistance, vision and pigmentation in NXC were preliminarily screened.4. The results provided theoretical guidance for further research on the genetic resource protection and utilisation of NXC.

Transcriptome analysis of long non-coding RNA associated with embryonic muscle development in chickens.

1. Skeletal muscle is an important component of chicken carcass. In chickens, the number of muscle fibres is fixed during the embryonic period, and muscle development during the embryonic period determines the muscle development potential after hatching.2. Beijing-You (BY) and Cornish (CN) chickens show completely different growth rates and body types, and two breeds were used in this study to explore the role of lncRNAs in muscle development during different chicken embryonic periods. A systematic analysis of lncRNAs and mRNAs were conducted in the pectoral muscle tissues of BY and CN chickens at embryonic days 11 (ED11), 13 (ED13), 15 (ED15), 17 (ED17), and 1-day-old (D1) using RNA-seq. A total of 4,104 differentially expressed transcripts (DETs) were identified among the five stages, including 2,359 lncRNAs and 1,745 mRNAs.3. The number of DETs between the two breeds at ED17 (1,658 lncRNAs and 1,016 mRNAs) was much higher than the total number of DET at all the other stages (692 lncRNAs and 729 mRNAs), indicating that the two breeds show the largest difference in gene regulation at ED17.4. Correlation analysis was performed for all differentially expressed lncRNAs and mRNAs during the five periods. Forty-three, cis interaction pairs of lncRNA-mRNA related to chicken muscle development were predicted. The expression of four pairs was verified, and the results showed MSTRG.12395.2-FGFBP2 and MSTRG.18590.6-FMOD were significantly up-regulated in CN at ED11 compared to BY and might be important candidate genes for embryonic muscle development.

[Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases].

Objective: To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. Methods: This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results: After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group (P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups(P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions: PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.

[Safety and efficacy of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis].

Objective: To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis. Methods: A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant (P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation (P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups (P>0.05). Conclusions: The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

[Clinical evaluation methods for craniovertebral junction abnormalities].

Craniovertebral junction malformation is a congenital malformation located in the foramen magnum and upper cervical spine, including bone and nerve malformation, resulting in motor and sensory disorders, cerebellar and lower cranial nerves, etc. The evaluation methods of clinical symptoms and efficacy of craniovertebral junction malformation are important for the surgical indications and effects, mainly including the evaluation of clinical symptoms and the quality of life. At present, the commonly used methods in clinical work and literature are the Japanese orthopaedic association scores, visual analogue scales, 36-item short-form health survey, etc. Most of these clinical evaluations are not aimed at craniovertebral junction diseases but focus on the description of a certain type of clinical symptoms. Chicago Chiari outcome scale and syringomyelia outcome scale of Xuanwu hospital are dedicated to Craniovertebral junction malformation, but more clinical studies are needed to prove their effectiveness. Based on the literature reports, this article reviewed the previous clinical evaluation methods of craniovertebral junction malformation and discusses their applications and limitations.

[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].

Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

[The measurement and application of imaging evaluation parameters for cranio-cervical junction osseous and neural abnormalities:a review].

Cranio-cervical junction (CVJ) anomalies encompass a spectrum of bone,soft tissue,and neural structural abnormalities,including basilar invagination,platybasia,atlantoaxial dislocation,tonsillar herniation,and occipito-cervical fusion.Given the frequent coexistence of these anomalies and the intricate anatomical variations involved,precise imaging techniques and evaluation parameters are crucial for accurate disease characterization and treatment assessment.Since the 1930s,various parameters,such as the McRae line,Chamberlain line,Wackenheim line,and clivo-axial angle,have been widely employed for evaluating basilar invagination and platybasia.The advent of MRI and CT has further expanded the repertoire of parameters,including sagittal tilt,coronal tilt,medullary spinal angle,and intricate multi-axis evaluation systems.In this review,we summarize the relevant imaging parameters and their corresponding measurement techniques from previous literature,emphasizing high-sensitivity,consistent,and evidence-based parameters.This study aims to provide valuable insights for the imaging evaluation of CVJ anomalies.

[Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection].

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

[Effect of pancreatic extracorporeal shock wave lithotripsy on chronic pancreatitis stones].

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.

[Surgical treatment strategy for difficult-reducible atlantoaxial dislocation].

Objective: To discuss the surgical strategy for difficult-reducible atlantoaxial dislocation. Methods: Clinical data of 82 patients with difficult-reducible atlantoaxial dislocation underwent surgical treatment in the Department of Neurosurgery, Xuanwu Hospital from January 2018 to February 2019 were retrospectively reviewed. Total of 32 men and 50 women were included, with a mean age of (41.8±12.9) years. Most cases (n=80) were treated with one-staged posterior atlantoaxial joint distraction and cage implantation, a few (n=2) underwent ventral decompression. All cases were followed up, postoperative improvement of clinical symptoms and radiology parameters were analyzed. Results: Of the patients, 80 cases (97.6%) received one-staged posterior atlantoaxial joint distraction and cage implantation; lateral facet joint bony fusion was found in 4 patients and was cut off with an osteotome. Transoral odontoidectomy was performed in 2 cases (2.4%) with fused atlanto-odontoid joint. All the patients were followed-up for (18.6±7.3) months. Postoperative CT showed complete reduction of ADI was achieved in 60 patients (75.0%). The ADI decreased significantly after the operation [(2.1±1.4) mm vs (5.0±1.5) mm, P<0.05]. The postoperative vertical distance between odontoid process and the Chamberlain line decreased significantly when compared with that before the operation [(3.9±3.8) mm vs (10.2±5.2) mm, P<0.05]. The mean JOA score at 6 months post operation improved significantly than that before the operation (13.7±1.5 vs 11.2±1.7, P<0.05). Seventy-five patients (93.8%) had atlantoaxial intra-articular bony fusion at 1 year follow-up. Conclusion: Most difficult-reducible atlantoaxial dislocations can be managed well by posterior one-staged atlantoaxial joint distraction and Cage implantation.

[Posterior atlanto-axial intraarticular distraction technique as revision surgery to treat atlanto-axial dislocation associated with basilar invagination].

Objective: To examine the effect of posterior atlanto-axial intraarticular distraction technique as revision surgery for failed posterior fossa decompression in patients with basilar invagination(BI) and atlanto-axial dislocation(AAD). Methods: The clinical data of 13 cases of AAD accompanied with BI treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical University were retrospectively analyzed. There were 3 males and 10 females,aged (42.6±9.5) years (range:30 to 63 years). All cases had assimilation of atlas and once underwent posterior fossa decompression. Anterior tissue was released through posterior approach followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line(DCL),clivus-canal angle(CCA) and the length of syrinx were collected. Paired sample t test was used to compared the data before and after operation. Results: All patients underwent surgery successfully, the mean surgical time was (187.7±47.4) minutes (range from 116 to 261 minutes). Twenty occipital condyle screws, 26 C2 pedicle screws and 3 occipital plates were implanted. Clinical symptoms improved in all patients. Twelve patients had complete reduction of basilar invagination and atlanto-axial dislocation, 1 achieved near completely reduction of basilar invagination. The postoperative ADI, DCL and CCA significantly improved((4.3±1.1) mm vs. (1.8±0.8) mm, (11.7±5.0) mm vs. (6.4±2.8) mm, (142.4±7.9)° vs. (133.3±7.9)°, all P<0.01).There were 5 cases with syringomyelia before surgery, and shrinkage of syrinx was observed 1 week after surgery in all cases. Eight patients achieved bone fusion 3 months after surgery, all patients achieved bone fusion 6 months after surgery. The JOA score increased from 12.8±2.3 before surgery to 14.8±1.3 one year after surgery, with statistically significant difference (t=4.416, P<0.01).No implant failure, spacer subsidence and infection were observed. Conclusion: In cases of failure posterior fossa decompression of basilar invagination and atlanto-axial dislocation, using posterior atlanto-axial intraarticular distraction and cantilever technique with cage implantation could achieve complete reduction and symptomatic relief.

[Analysis of clinical features of multiple myeloma with t(8;14)(q24;q32)].

Objective: To investigate the clinical manifestations and prognosis of multiple myeloma (MM) patients with t(8;14)(q24;q32). Methods: The clinical data of MM patients with G-banding results from 2004 to 2009 in Hematology Department of People's Hospital of Peking University were retrospectively analyzed. The general data, M protein related examination, cytogenetics data, therapeutic regimen and response evaluation of MM patients with t(8;14)(q24;q32) were collected. Results: Of all newly diagnosed multiple myeloma patients, the number of patients who had G-banding results was 940, among which 265 had abnormal karyotype in G-banding, accounting for 28.19%. The incidence of t(8;14)(q24;q32) detected by G-banding in MM patients was 0.85%(8/940), t(8;14)(q24;q32) accounted for 3.02%(8/265) of all choromosome abnormalities detected by G-banding. Seven of eight patients were male with a median age of 63.5(56-76) and the immunoglobulin sub-types seven in eight patients were lambda. All eight patients had DS stage Ⅲ at the time of initial diagnosis. FISH detection of these eight patients showed six patients(75%) with 1q21 amplification, and five patients(62.5%) with G-banding results showed abnormal chromosome 1. Among the eight patients, the number of patients reached complete response ,very good response and partial response were separately four, one and two, and the overall response rate(ORR) was 87.5%. After the median follow-up 35 months(23-65months), 2 patients died, and the OS of the dead patients exceeded 5 years. Conclusions: Patients with t(8;14)(q24;q32) accounted for 0.85% of the total who have the results of G banding in our hospital. Of our 8 patients, the light chain sub-type Lambda was more than Kappa, the patients were more common in males, accompanied by 1q21 amplification and chromosome 1 abnormality. The tumor load was high at the time of diagnosis, but the overall response to treatment was fair.

[Effects of ursolic acid on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure].

Objective: To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure. Methods: Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 µg/m3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results: After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group (P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1ß, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion: UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial.

BACKGROUND: There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy. METHODS: FORTIFY is a phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance withdrawal study across 273 clinical centres in 44 countries across North and South America, Europe, Oceania, Africa, and the Asia-Pacific region that enrolled participants with clinical response to risankizumab in the ADVANCE or MOTIVATE induction studies. Patients in ADVANCE or MOTIVATE were aged 16-80 years with moderately to severely active Crohn's disease. Patients in the FORTIFY substudy 1 were randomly assigned again (1:1:1) to receive either subcutaneous risankizumab 180 mg, subcutaneous risankizumab 360 mg, or withdrawal from risankizumab to receive subcutaneous placebo (herein referred to as withdrawal [subcutaneous placebo]). Treatment was given every 8 weeks. Patients were stratified by induction dose, post-induction endoscopic response, and clinical remission status. Patients, investigators, and study personnel were masked to treatment assignments. Week 52 co-primary endpoints were clinical remission (Crohn's disease activity index [CDAI] in the US protocol, or stool frequency and abdominal pain score in the non-US protocol) and endoscopic response in patients who received at least one dose of study drug during the 52-week maintenance period. Safety was assessed in patients receiving at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03105102. FINDINGS: 712 patients were initially assessed and, between April 9, 2018, and April 24, 2020, 542 patients were randomly assigned to either the risankizumab 180 mg group (n=179), the risankizumab 360 mg group (n=179), or the placebo group (n=184). Greater clinical remission and endoscopic response rates were reached with 360 mg risankizumab versus placebo (CDAI clinical remission was reached in 74 (52%) of 141 patients vs 67 (41%) of 164 patients, adjusted difference 15% [95% CI 5-24]; stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of 141 vs 65 (40%) of 164, adjusted difference 15% [5-25]; endoscopic response 66 (47%) of 141 patients vs 36 (22%) of 164 patients, adjusted difference 28% [19-37]). Higher rates of CDAI clinical remission and endoscopic response (but not stool frequency and abdominal pain score clinical remission [p=0·124]) were also reached with risankizumab 180 mg versus withdrawal (subcutaneous placebo; CDAI clinical remission reached in 87 [55%] of 157 patients, adjusted difference 15% [95% CI 5-24]; endoscopic response 74 [47%] of 157, adjusted difference 26% [17-35]). Results for more stringent endoscopic and composite endpoints and inflammatory biomarkers were consistent with a dose-response relationship. Maintenance treatment was well tolerated. Adverse event rates were similar among groups, and the most frequently reported adverse events in all treatment groups were worsening Crohn's disease, arthralgia, and headache. INTERPRETATION: Subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease. FUNDING: AbbVie.

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials.

BACKGROUND: Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. METHODS: ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. FINDINGS: Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. INTERPRETATION: Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. FUNDING: AbbVie.

[Connective tissue diseases and the liver injury].

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.

First live birth in China after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.