Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective:To investigate the early and mid-term outcomes of aortic endovascular remodeling device (AERD) for Stanford type A aortic dissection (TAAD) in type Ⅱhybrid surgery, and to evaluate its clinical efficacy.Methods:46 patients with TAAD, including 14 females and 32 males, participated in the single-center clinical trial of West China Hospital of Sichuan University and underwent type II hybrid surgery (Bentall / ascending aorta replacement + AERD implantation) from February 2021 to October 2023. The safety and efficacy of AERD in type Ⅱ hybrid surgery for TAAD were estimated by clinical indicators (postoperative mortality, cardiovascular and cerebrovascular accidents, paraplegia, ischemia), and blood flow condition (volume of the true and false lumen, and suprachial branches).Results:Three patients (6.52%) died during the follow-up period, and the operation-related mortality was 4.35% (2/46). The remaining 43 patients were followed up for an average of (25.53±9.60) months. There were two cases (4.35%) of stroke after the operation, and paraplegia, acute renal insufficiency, and other severe complications were not noticed. The blood flow of the superior branch of the aortic arch was unobstructed, and there was no significant difference in the blood flow of the branch before the operation and at each follow-up time point. Compared to the pre-operation, the true lumen volume of the stent part increased by 59.0% and the false lumen volume decreased by 82.4%.Conclusion:AERD is a safe and effective alternative in type II hybrid surgery for acute TAAD, which is helpful in improving perioperative and short- and long-term survival rates and clinical outcomes.

Objective:To analyzed the 3-year follow-up results in a single center to evaluate the mid-term clinical efficacy of aortic endovascular remodeling device(AERD).Methods:From January 2019 to June 2019, 18 patients with residual aortic dissection after proximal repair of acute aortic dissection were treated with AERD in our heart center of West China Hospital of Sichuan University. They were followed up for 3 years after surgery and underwent vascular enhanced CT review. The primary outcome of our study included all-cause mortality and stent-related mortality. Secondary outcome included branch patency rate, reoperation rate and the incidence of serious adverse events. Morphological measures assessed the effectiveness of AERD in treating residual distal dissection.Results:17 patients completed the 3-year follow-up, and 1 was lost to follow-up. There was no stent-related death, branch artery occlusion, or new serious adverse events. 12 patients completed vascular enhanced CT review, the true lumen was significantly expanded and the false lumen was reduced considerably at 3-year follow-up, true lumen volume, (52.39±22.32)cm 3 vs. (74.34±14.64) cm 3( P<0.01), false lumen volume(50.42±25.44) cm 3 vs. (32.32±31.75)cm 3( P<0.01). Increased true lumen diameter and area ( P<0.001) and decreased false lumen diameter( P<0.001) were significantly different from those before operation, especially in the level below the renal artery and 5 cm below the renal artery. Conclusion:The mid-term effect of AERD in treating distal residual dissection is satisfactory, and it promoted positive distal aorta remodeling with safety and effectiveness.

Objective Using healthy female reproductive-age rhesus macaques as the research subjects,we explored the correlation between menstrual cycle abnormalities and gut microbiota composition by using 16S rRNA metagenomic sequencing.Methods Twenty-seven healthy female rhesus macaques were divided into regular menstrual and irregular menstrual groups.Fecal samples were collected at follicular phase(FP),ovulation phase(OP)and luteal phase(LP)of the two groups.The structure and diversity of bacterial flora in different physiological periods were analyzed and compared between the two groups.Results At the phylum level,Firmicutes,Bacteroidetes,and Proteobacteria dominated the sample flora in the follicular,luteal,and ovulatory phases of the rhesus macaques in both the regular and irregular groups,with a combined percentage of more than 98% .At the genus level,the genus Prevotella_9,Ruminococcaceae_UCG-002,Lactobacillus,Prevotella_2,Phascolarctobacterium,Ruminococcaceae_UCG-005,Streptococcus,Blautia,Prevotellaceae_NK3B31_group,Rikenellaceae_RC9_gut_group were dominant.In the luteal phase the percentage of Firmicutes was higher in the regular group than in the irregular group,while the opposite was true for Bacteroidetes.Spirochaetes were higher in the regular group than in the irregular group at all 3 stages(P＜0.05).Conclusion There were some differences in intestinal microbial composition between the two groups of macaques with regular and irregular menstrual cycles,which provided some reference for the study of intestinal bacteria and ovulation disorders.

Objective To evaluate the clinical efficacy of two-stage retrograde hybrid repair for acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome. Methods From May 2019 to December 2022, the patients presented with acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome treated in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University were enrolled. After preoperative evaluation, all patients underwent priority emergency interventional surgery to improve distal malperfusion, and then underwent two-stage hybrid surgery to repair proximal aortic lesions. The perioperative clinical and imaging data were retrospectively analyzed. Results Five patients were collected, including 4 males and 1 female, with a median age of 58 years. The main manifestations were lower limb ischemia and renal insufficiency in 3 patients, and poor intestinal perfusion in 2 patients. All patients were given priority to interventional surgery to implant graft stents or bare stents and necessary branch artery intervention, and then successfully performed two-stage hybrid surgery, including type Ⅰhybrid surgery for 2 patients, type Ⅱ hybrid surgery for 1 patient and type Ⅲ hybrid surgery for the other 2 patients, with a success rate of 100.0%. All patients were discharged successfully, and the function of the organs with poor perfusion returned to normal. Only 1 patient recovered to grade 4 muscle strength of the diseased lower limbs upon discharge. No adverse events such as amputation, exploratory laparotomy and intestinal resection or long-term hemodialysis occurred. Conclusion The application of two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome is safe and effective, and is helpful to improve the perioperative survival rate, and clinical outcomes of such patients.

Objective To investigate the clinical efficacy of transjugular intrahepatic portosystemic shunt(TIPS)combined with indwelling catheter-directed thrombolysis for the treatment of portal vein thrombosis(PVT).Methods The clinical efficacy of 307 patients with portal hypertension complicated by PVT,who received successful TIPS combined with indwelling catheter-directed thrombolysis at the Affiliated Beijing Shijitan Hospital of Capital Medical University of China between January 2016 and December 2019,were retrospectively analyzed.Before and after TIPS,the inferior vena cava pressure(IVCP)and portal vein pressure(PVP)were measured,and the pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis portal pressure gradient(PPG,PPG=PVP-IVCP)was separately calculated.Reexamination of portal venography DSA was performed to determine the degree of PVT disappearance and whether the shunt was unobstructed.All patients were followed up for one year.Results The pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis mean PPG was(24.50±6.91)mmHg,(18.51±5.11)mmHg,and(10.17±3.97)mmHg,respectively.The post-thrombolysis mean PPG was strikingly lower than the pre-thrombolysis values,the differences were statistically significant(P＜0.001).Among the 307 patients,complete disappearance of PVT was observed in 221(72.3%),remarkable reduction of PVT in 86(27.7%),and no invalid result was seen.The patients having complete patency of the shunt flow accounted for 85.7%of the 307 patients(261/307),and the patients having partial patency of the shunt flow accounted for 14.3%of the 307 patients(46/307).Forty-two patients developed complications,and no death occurred.All patients were followed up for one year,and the main clinical symptoms were improved or completely disappeared.Among the 307 patients,an increase in thrombus volume was found in 17(5.5%)when compared to their postoperative values,which returned to the first-time postoperative level after local treatment of the thrombus via the TIPS shunt combined with catheter-directed thrombolysis.Within one year after TIPS and thrombolysis,overt hepatic encephalopathy(OHE)occurred in 54 patients(17.6%,54/307).One patient died of hepatic failure 9 months after TIPS,another patient died of cerebral hemorrhage 11 months after TIPS,and all the remaining patients were alive.Conclusion For patients with portal hypertension complicated by PVT,TIPS combined with indwelling catheter-directed thrombolysis is clinically safe and effective.The standardized,systematic management of the whole therapeutic process should be strengthened.(J Intervent Radiol,2024,32:22-27)

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Objective To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province. Methods Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects’ demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5. Results A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07_BC (52.1%) and CRF01_AE (30.4%) as predominant subtypes, followed by CRF08_BC (4.9%), CRF55_01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85_BC (1.7%), CRF59_01B (0.3%) and CRF65_CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59_01B subtype, followed by in CRF08_BC, B, C, CRF01_AE, CRF07_BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ² = 45.002, P < 0.05). Conclusions There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.

Objective:To evaluate the various wire tension belt ventral compression wiring technologiesfor treating several types of femoral greater trochanter fractures in total hip replacement, according to the different types of greater trochanter of femur fractures.Methods:From March 2013 to June 2019, a total of 1 280 cases of primary total hip arthroplasty were completed in our hospital, 21 patients with greater trochanter fractures were identified in total hip replacement. There were 11 males and 10 females with an average age of 65.81±6.45 years (range 42-76 years). All of them were unilateral. There were 11 cases on the left and 10 cases on the right. There were 11 cases of osteoarthritis secondary to hip dysplasia, 4 cases of hip osteoarthritis, 4 cases of aseptic necrosis of femoral head and 2 cases of femoral neck fracture. Different wire tension belt ventral compression wiring technologies were used for each fracture type. Harris hip function score, Parker activity score, and visual analogue scale (VAS) score of hip pain were evaluated during follow-up. X-ray films were taken to evaluate the fracture healing, prosthesis position, loosening and dislocation.Results:Three new fracture types were proposed: A transverse fracture from the greater trochanter tip to the base (4 cases); B oblique fracture from the greater trochanter tip to the base (according to the fracture line direction, type B was further divided into types B1 (4 cases) and B2 (6 cases); and C fracture line from the greater trochanter to subtrochanteric plane (7 cases). Among the 21 patients, one died at an early stage, two were lost during follow-up, and 18 were followed up for an average of 30.7±7.6 months. In 18 patients, the mean operation time was 110.0±20.0 min, and the mean intraoperative blood loss was 356.9±115.7 ml. The patients' Harris score was 35.26±5.52 at the preoperative, 65.7±6.42 at the 3 months after operation, and 87.75±6.21 at the final follow-up. The difference was statistically significant ( F=377.23, P<0.001). The patients' Parker score was 2.17±0.98 at the preoperative, 5.94±1.11 at the 3 months after operation,and 8.01±0.77 at the final follow-up. The difference was statistically significant ( F=170.96, P<0.001). The patients' VAS score was 6.22±1.11 at the preoperative, 2.61±0.92 at the 3 months after operation, and 1.28±0.67 at the final follow-up. The difference was statistically significant ( F=139.71, P<0.001). Deep vein embolism, heterotopic ossification was noted in one and another patient, respectively. The patient with non-union refused reoperation and had a broken steel wire, lower-limb limp, and no notable pain at the 12-month follow-up examination. Radiographs of 17 patients showed good location of the femoral prosthesis and no chronic pain. Conclusion:Different types of greater trochanter fractures in total hip arthroplasty were proposed, using different wire tension belt ventral compression wiring technologies for the various types of femoral greater trochanter fractures during total hip replacement can improve clinical outcomes.

OBJECTIVE：To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS ：The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ，LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3，respectively. RESULTS ： Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL（R2＞0.996 7）. The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12％ （n＝6 or n＝3）. Accuracies were 90.92％-108.00％（n＝6 or n＝3）. The average extraction recoveries were 87.51％-100.00％（RSD＜8％，n＝6）. The average matrix effects were 96.66％-99.93％（RSD＜5％，n＝6）. The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS ：The method is simple ，accurate and specific ，and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.