Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Objective To explore the relationships of MRI manifestations of pericruciate ligament fat pad(PCFP)with the severity of knee osteoarthritis(KOA).Methods Fifty patients with MRI diagnosed KOA(KOA group)and 30 healthy subjects(control group)were retrospectively included.Signal intensity changes of PCFP,infrapatellar fat pad(IPFP),quadriceps fat pad(QFP)and prefemoral fat pad(PFP)were observed,and the maximum cross-sectional areas were obtained.The severity of KOA was assessed,including knee cartilage injury,anterior cruciate ligament tear,bone marrow lesion(BML),meniscal injuries and Park classification.MRI parameters of fat pad were compared between groups,and correlations of PCFP MRI parameter and other fat pad MRI parameters with the severity of KOA were analyzed.Results Signal change grade of IPFP and PCFP were significant different between groups(both P＜0.05),and the maximum cross-sectional area of IPFP and the thickness of PFP patellofemoral in KOA group were smaller than,while the maximum cross-sectional area of PCFP in KOA group was larger than that in control group(all P＜0.05).The signal change grade of PCFP was positively related to signal change grade of IPFP(rs=0.557)but negatively related to PFP interpatellofemoral thickness(rs=-0.651).The maximum cross-sectional area of PCFP was positively related to the maximum cross-sectional area of IPFP,PFP and QFP,also to the QFP occupancy effect(n=0.314 to 0.368).The signal change grade of PCFP was positively related to the cartilage injuries of knee compartments(medial and lateral patellofemoral joints,the femoral medial and lateral,the tibial medial and lateral)(rs=0.502 to 0.735),and the maximum cross-sectional area of PCFP was related to the lateral femoral cartilage injury(rs=0.305).In addition,the signal change grade of PCFP was positively related to tear of anterior cruciate ligament,BML,medial meniscus tears,lateral meniscus tears,medial meniscus extrusion,exudative synovitis and Park grading(rs=0.425 to 0.789),while the maximum cross-sectional area of PCFP was positively related to BML(rs=0.313).Conclusion MRI signal changes of PCFP could indicate KOA,and the grade of signal changes was correlated with the severity of KOA.

BACKGROUND:The key to preventing the recurrence of intrauterine adhesions is to reconstruct the endometrium with normal function.The latest breakthrough in the treatment of recurrent intrauterine adhesions in and outside China is the use of degradable materials to prepare hydrogels to prevent the recurrence of adhesions. OBJECTIVE:To review the research advance in hydrogel-promoted endometrial repair in intrauterine adhesions. METHODS:PubMed,Web of Science,China National Knowledge Infrastructure(CNKI),and WanFang databases were searched systematically,with the keywords"intrauterine adhesions,endometrial injury,endometrium regeneration,hydrogel"in Chinese and English.Relevant articles published in each database from January 1990 to March 2023 were collected. RESULTS AND CONCLUSION:In recent years,research on hydrogel-promoted endometrial repair in uterine adhesions in and outside China has made some progress and plays an important role in the prevention and treatment of intrauterine adhesions and the promotion of endometrial repair:(1)As an important carrier in tissue engineering,hydrogel itself has excellent biocompatibility,biodegradability and three-dimensional network structure,which can be better applied in the treatment of intrauterine adhesions.(2)The hydrogel-based carrier system can promote the proliferation and differentiation of endometrial epithelial cells by transporting drugs/biologics/stem cells,and restore normal uterine morphology to prevent adhesion recurrence.(3)Hyaluronic acid hydrogels can not only meet good biocompatibility,but also promote the proliferation and differentiation of endometrial epithelial cells,and will be hydrolyzed by corresponding enzymes in utero,without affecting the normal metabolism of the body.They are currently commonly used uterine anti-adhesion agents in the clinic and are also the most commonly used hydrogel carriers in tissue engineering research.(4)Poloxamer hydrogel with excellent temperature-sensitive properties can rapidly gelate into the body,quickly form a physical barrier,and can play a slow-release effect on carrying substances and provide a platform for cell growth/adhesion.(5)There are broad prospects for the preparation of therapeutic hydrogels using materials with different characteristics,such as temperature-sensitive hydrogels,pH-responsive hydrogels and photosensitive hydrogels,but there are still many problems to be solved,such as the safety of the hydrogel system,whether the degradation products cause immune reactions,and whether they have an impact on the normal body's menstrual period.A large number of animal experiments and clinical trials are needed to verify its safety and efficacy,and continuously improve the treatment strategy.

Objective To evaluate the effect of modified and traditional subcostal and anterior quadratus lumborum block on postoperative analgesia in patients with laparoscopic nephrectomy.Methods 46 patients underwent laparoscopic nephrectomy.They were randomly divided into two groups:traditional subcostal quadratus lumborum block(group T)and modified subcostal quadratus lumborum block(group M),with 23 cases in each group.Before anesthesia induction,the T group was subjected to the traditional subcostal and anterior quadratus lumborum block under ultrasound guidance,and the M group was subjected to the modified subcostal quadratus lumborum block under ultrasound guidance.All were given 0.5％ropivacaine 20 ml.Patients controlled intravenous analgesia(PCIA)was performed in both groups.The dermatomal levels of 5min,10 min and 15min after block was recorded.VAS pain scores at rest and cough were recorded at 6,24 and 48 h after the block.The dosage of Sufentanil,the number of analgesic pump compressions and the flurbiprofen rescue were recorded 24 h after surgery.Results The number of block plane segments in group M at 5,10 and 15 minutes after block were 6(4,8),8(6,9)and 8(6,9),respectively,which were significantly more than the T group[4(2,6),6(2,9),6(2,9)](P＜0.05).The VAS pain scores of patients in group M were(1.6±0.5)points at rest and(3.7±0.6)points at cough 6 hours after block,24 hours after the block were(2.3±0.4)points and(3.4±0.4)points,respectively,48 hours after the block were(2.5±0.8)min and(3.2±0.7)min,respectively.The VAS pain scores of and at rest and cough 6 hours after block in T group were(2.5±0.7)points and(5.6±0.8)points,respectively,24 hours after the block were(3.1±0.5)points and(4.5±0.7)points,respectively,48 hours after the block were(3.3±0.6)min and(4.2±0.6)min,respectively.Group M was lower than group T(P＜0.05).In group M,the dosage of sufentanil,the times of analgesic pump and the rate of analgesic relief 24 hours after operation were(23.1±4.3)μg,5(4,7)times and 4.3％,respectively,which were significantly lower than those in T group[(34.7±6.8)μg,11(9,12)times,21.7％](P＜0.05).Conclusion Ultrasound-guided modified subcostal and anterior quadratus lumborum block has better analgesic effect than traditional technique in patients undergoing laparoscopic nephrectomy,which can reduce the amount of postoperative analgesic drugs and effectively relieve postoperative pain.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

新冠病毒感染疫情严重威胁着世界各国人民的生命健康。目前，对病毒感染的防治研究主要集中在抑制病毒与分子受体的结合上。AXL作为新发现的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）受体，在协助病毒感染人体呼吸系统中发挥着重要作用，是未来临床干预的潜在靶点。本研究对已发表的单细胞测序数据进行整理和分析，发现AXL在年轻人肺细胞中的表达水平明显高于老年人。人胚肺二倍体成纤维细胞（2BS）是衰老研究的公认细胞株。本文采用2BS细胞构建复制性细胞衰老模型，发现年轻细胞中AXL的蛋白水平明显高于衰老细胞，据此推测年轻人感染的风险可能更高，需要注意防护。我们发现一种羊栖菜褐藻多糖硫酸酯组分（SFW-3）可显著下调年轻2BS细胞中AXL的表达水平，表明SFW-3具有一定的抗SARS-CoV-2感染的研究价值，同时表明2BS细胞株也可作为潜在的SARS-CoV-2体外感染模型。
Humans ; SARS-CoV-2 ; Sargassum/metabolism* ; Diploidy ; Sulfates/metabolism* ; COVID-19 ; Polysaccharides/pharmacology* ; Lung

Micronutrients are important factors affecting the immune system. Micronutrients contribute to maintaining the normal functions of immune system through maintaining the integrity of skin and mucosa, regulating the activity of cytokines, and mediating the proliferation and differentiation of T cells and B cells. Human immune system changes at different stages of growth and development, and micronutrient deficiency can impair the immune system and increase the susceptibility to respiratory infections. Therefore, maintaining the optimal nutritional status is beneficial for the immune system to prevent respiratory infections. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection is one of the respiratory infectious diseases that is of most concern recently. Micronutrient supplementation has been shown to have positive effects on the prevention of, symptom relief of and recovery from SARS-Cov-2 infection. Further studies are needed to systematically evaluate the effects of micronutrients on immunity and respiratory infections, and to identify the appropriate timing and dosage.

ObjectiveTo explore the features and assessment for far space neglect in left spatial neglect patients after right brain stroke. MethodsFrom January to October, 2021, 30 left unilateral spatial neglect (USN) patients after right stroke (patients, n = 30) from Beijing Bo'ai Hospital and healthy volunteers matching with gender, age and level of education (controls, n = 30) were evaluated with line cancelation (LC), star cancelation (SC) and line bisection (LB) tests, nearly and far away. The 25 controls were evaluated with LB on the second day. ResultsNo line or star was omissed in the controls. Both the deviation and percentage were more in the patients than in the controls (|t| > 4.319, P < 0.001). Both the deviation and percentage were less different for all the test (|Z| < 1.638, t = -1.282, P > 0.05) between nearly and far away, except the deviation of LB (t = -4.994, P < 0.001). The ICC of test-retest was above 0.462 (P < 0.01). ConclusionRight brain stroke patients with USN may present far spatial neglect, which can be assessed with LB.

Objective:To investigate the safety and effectiveness of Willis covered stent in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.Methods:A retrospective analysis was performed. Six patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection admitted to the 3 hospitals from May 2016 to December 2019 were chosen; their clinical data were collected. The surgical processes and complications were concluded, and the prognoses were evaluated by modified Rankin scale (mRS).Results:One patient was treated with intraoperative simple tamponade compression for hemostasis, and died for massive intracranial hemorrhage 2 weeks after surgery. Five patients were occluded by Willis covered stents; the occluded success rate was 100% but ophthalmic arteries were blocked in all. During the perioperative period, diabetes insipidus occurred in one patient and incomplete oculomotor paralysis occurred in one patient; 5 patients were followed up for 3-12 months: MRI indicated subtotal resection of tumor in 4 patients and total resection in one patient, no new bleeding or ischemic stroke events occurred in these 5 patients, and the prognosis was good.Conclusion:Willis covered stent is safe and effective in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.