[Transverse sinus blood flow characteristics of pulsatile tinnitus with dehiscent sigmoid plate based on 4D flow MRI].

Objective: To investigate the hemodynamic characteristics of transverse sinus with sigmoid sinus wall dehiscence (SSWD) of pulsatile tinnitus (PT) based on 4D flow MRI. Methods: Retrospective analysis was performed on all patients admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2021 for dehiscent sigmoid plate pulsatile tinnitus. A total of 26 patients (sides) who met the criteria and underwent 4D flow MRI were included. A total of 26 subjects (46 sides), matched 1∶1 according to gender and age, were included in the normal healthy control group. Nonparametric rank sum test, Student's t test, and ANOVA were performed by SPSS 19.0 software. Binary Logistic regression was applied to the data with statistical significance. Results: There were more patients with dominant drainage on the affected side in PT group than in control group (73.1% vs. 42.3%). The incidence of transverse with a focal intraluminal filling defect and tapered stenosis was higher than that in control group (21.7% vs. 69.2%; 17.4% vs. 42.3%). Average through-plane velocity and maximum through-plane velocity in PT group were higher than those in control group [(33.75±13.88) cm/s vs. (15.84±7.21) cm/s; (93.19±33.55) cm/s vs. (40.40±14.40) cm/s]. The middle part and proximal end of Flowavg (ml/s) in PT group were larger than those in control group [4.69 (2.87; 5.62) ml/s vs. 2.76 (1.67; 4.99) ml/s; 3.41 (2.16; 5.47) ml/s vs. 2.67 (1.68; 4.41) ml/s]. In control group, the velocity of transverse sinus changed relatively gently, while in PT group, the velocity of proximal sinus increased significantly. Binary Logistic regression showed that SSWD PT was independently correlated with proximal maximum flow velocity [OR=1.086(1.029-1.146),P=0.003]. Conclusion: 4D flow MRI showed that the dominant drainage and higher velocity at the proximal end of the transverse sinus might be an important hemodynamic characteristics of dehiscent sigmoid plate pulsatile tinnitus.

Supplementing pigeon grit with acidifier improves metabolism and the reproductive performance of breeding pigeons as well as the development of growth performance of squabs.

1. This study evaluated the effectiveness of different types of acidifiers on reproductive performance, body weight loss and plasma biochemical indices of breeding pigeons as well as on growth performance, carcass characteristics, meat quality and plasma biochemical indices of squabs.2. In a 45 d trial, 144 pairs of European white Mimas pigeons were selected and randomly divided into three experimental groups. Three groups of pigeons were fed plain pigeon grit (NC), pigeon grit supplemented with 5% single acidifier (SAG) and pigeon grit supplemented with 5% combined acidifiers (CAG).3. Supplementing with SAG and CAG significantly increased the weight gain in male pigeons from 1-12 d of incubation. However, SAG and CAG had no significant effect on the feed intake of breeding pigeons during incubation, but significantly increased total feed intake of breeding pigeons during the lactation period. Breeder pigeons fed SAG and CAG had significantly higher egg-laying rate at 40 d. In addition, feeding SAG and CAG significantly increased growth rate and slaughter weight of squabs, but SAG reduced the diameter of pectoral muscle fibres. Biochemical indices showed that feeding SAG and CAG improved metabolism and increased the liver function of breeder pigeons and squabs.4. In conclusion, supplementing pigeon grit with acidifiers increased feed intake of breeding pigeons during lactation, protected liver function, enhanced reproductive performance and promoted the growth and development of squabs.

Supplementation with single acidifier and combined acidifier is healthy for both breeding pigeons and squabs.Supplementation with single acidifier and combined acidifier can improve the egg-laying rate of breeding pigeons.Supplementation with single acidifier and combined acidifier can improve the growth rate of squabs.Supplementation single acidifier and combined acidifier helps to protect the liver and reduce liver damage of breeding pigeons and squabs.

Short term air pollution exposure during pregnancy and associations with maternal immune markers.

BACKGROUND: Air pollution exposure during pregnancy has been associated with numerous adverse pregnancy, birth, and child health outcomes. One proposed mechanism underlying these associations is maternal immune activation and dysregulation. We examined associations between PM2.5 and NO2 exposure during pregnancy and immune markers within immune function groups (TH1, TH2, TH17, Innate/Early Activation, Regulatory, Homeostatic, and Proinflammatory), and examined whether those associations changed across pregnancy. METHODS: In a pregnancy cohort study (n = 290) in Rochester, New York, we measured immune markers (using Luminex) in maternal plasma up to 3 times during pregnancy. We estimated ambient PM2.5 and NO2 concentrations at participants' home addresses using a spatial-temporal model. Using mixed effects models, we estimated changes in immune marker concentrations associated with interquartile range increases in PM2.5 (2.88 µg/m3) and NO2 (7.82 ppb) 0-6 days before blood collection, and assessed whether associations were different in early, mid, and late pregnancy. RESULTS: Increased NO2 concentrations were associated with higher maternal immune markers, with associations observed across TH1, TH2, TH17, Regulatory, and Homeostatic groups of immune markers. Furthermore, the largest increases in immune markers associated with each 7.82 ppb increase in NO2 concentration were in late pregnancy (e.g., IL-23 = 0.26 pg/ml, 95% CI = 0.07, 0.46) compared to early pregnancy (e.g., IL-23 = 0.08 pg/ml, 95% CI = -0.11, 0.26). CONCLUSIONS: Results were suggestive of NO2-related immune activation. Increases in effect sizes from early to mid to late pregnancy may be due to changes in immune function over the course of pregnancy. These findings provide a basis for immune activation as a mechanism for previously observed associations between air pollution exposure during pregnancy and reduced birthweight, fetal growth restriction, and pregnancy complications.

Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

[Bronchoscopic intervention therapy for pulmonary mucormycosis with main bronchial occlusion: a case report].

Pulmonary mucormycosis is one of the most common types of mucormycosis. Tracheobronchial pulmonary mucormycosis primarily affects the tracheobronchial tree, causing lesions that can invade the airway mucosa and muscular layer, damaging the cartilage. It is characterised by acute onset, rapid progression, and high mortality rate, making clinical treatment challenging. This article reports the diagnosis and treatment of a patient with pulmonary mucormycosis complicated by left main bronchus occlusion. In addition to systemic treatment, which consisted mainly of an intravenous injection of amphotericin B combined with an oral suspension of posaconazole, the patient underwent multiple bronchoscopic interventions, including local infusion of amphotericin B under endoscopy, balloon dilation and silicone stent placement. After four months of comprehensive treatment, the therapeutic effect was satisfactory. This report demonstrates that bronchoscopic intervention therapy plays an important role in the comprehensive treatment of pulmonary mucormycosis, especially in preventing death from the progression to obstructive pneumonia.

[Efficiency of CNV-seq in detecting fetal DMD gene deletion or duplication in prenatal diagnosis].

Objective: To evaluate the diagnostic efficiency of copy number variation sequencing (CNV-seq) to detect the deletion or duplication of DMD gene in prenatal diagnosis. Methods: A retrospective analysis was carried out on the CNV-seq results of 34 544 fetuses diagnosed in the First People's Hospital of Yunnan Province from January 2018 to July 2023. A total of 156 cases of fetuses were collected, including Group 1:125 cases with family history of Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), and Group 2:31 cases with no family history but a DMD gene deletion or duplication was detected unexpectedly by CNV-seq. Multiplex ligation-dependent probe amplification (MLPA) was used as a standard method to detect the deletion or duplication. Consistency test was carried out basing on the results of CNV-seq and MLPA of all 156 cases. Results: Comparing to MLPA, CNV-seq had a coincidence rate of 92.3% (144/156) for DMD gene deletion or duplication, with a sensitivity and positive predictive value of 88.2%, with a specificity and negative predictive value of 94.3%, a missed detection rate of 3.8%, and a Kappa value of 0.839. CNV-seq missed 4 cases with deletions and 2 with duplications due to involved fragments less than 100 Kb, among 20 cases of deletions and 6 cases of duplications detected by MLPA in Group 1. In Group 2, the deletions and duplications detected by CNV-seq were 42% (13/31) and 58% (18/31), respectively, in which the percentage of duplication was higher than that in Group 1. Among those 18 cases with duplications, 3 cases with duplication locating in exon 42~67 were likely pathogenic; while 9 cases with duplication covering the 5' or 3' end of the DMD gene, containing exon 1 or 79 and with only one breakpoint within the gene, along with the last 6 cases with duplications locating at chrX: 32650635_32910000 detected only by CNV-seq, which might be judged as variants of uncertain significance. Conclusions: CNV-seq has a good efficiency to detect fetal DMD gene deletion or duplication in prenatal diagnosis, while a further verification test by MLPA is recommended. The duplications on chrX: 32650635_32910000, 5' or 3' end of DMD gene detected by CNV-seq should be carefully verified and assessed because those variants appear to be nonpathogenic polymorphisms.

Optimizing the indication of initial radioiodine oncolytic treatment for metastatic differentiated thyroid cancer by diagnostic 131I scan.

AIM: As a classic theranostic radiopharmaceutical, radioiodine (131I) has been utilized in the management of differentiated thyroid cancer (DTC) for more than 8 decades, and the refinement of its clinical practice has been raised recently. This study was conducted to evaluate the efficiency of a diagnostic (Dx) 131I scan in optimizing the indication of initial radioiodine oncolytic treatment (ROT) for metastatic DTC by predicting therapeutic outcomes. RESULTS: A total of 100 patients (Dx positive, n=29; Dx negative, n=71) were eligible for patient-based analysis. The matching rate was 83.0% between the Dx and the post-therapeutic scans (kappa = 0.648, P<0.001). The biochemical remission rate and structural shrinkage rate induced by the initial ROT in the Dx-positive group were, respectively, greater than those in the Dx-negative group (83.3% vs. 17.4%, P<0.001; 37.9% vs. 4.2%, P<0.001). Notably, the predictive values of positive Dx scans for ROT responsiveness and negative Dx scans for ROT nonresponsiveness reached up to 89.7% and 84.5%, respectively. CONCLUSION: This Dx scan approach seems viable in characterizing the 131I-avidity of metastatic DTC and plays a pivotal role in optimizing the indication of initial ROT for metastatic DTC.

CircNRCAM up-regulates NRCAM to promote papillary thyroid carcinoma progression.

PURPOSE: Papillary Thyroid Carcinoma (PTC) is the most prevalent subtype of Thyroid Carcinoma (THCA), a type of malignancy in the endocrine system. According to prior studies, Neural Cell Adhesion Molecule (NRCAM) has been found to be up-regulated in PTC and stimulates the proliferation and migration of PTC cells. However, the specific mechanism of NRCAM in PTC cells is not yet fully understood. Consequently, this study aimed to investigate the underlying mechanism of NRCAM in PTC cells, the findings of which could provide new insights for the development of potential treatment targets for PTC. METHODS AND RESULTS: Bioinformatics tools were utilized and a series of experiments were conducted, including Western blot, colony formation, and dual-luciferase reporter assays. The data collected indicated that NRCAM was overexpressed in THCA tissues and PTC cells. Circular RNA NRCAM (circNRCAM) was found to be highly expressed in PTC cells and to positively regulate NRCAM expression. Through loss-of-function assays, both circNRCAM and NRCAM were shown to promote the proliferation, invasion, and migration of PTC cells. Mechanistically, this study confirmed that precursor microRNA-506 (pre-miR-506) could bind with m6A demethylase AlkB Homolog 5 (ALKBH5), leading to its m6A demethylation. It was also discovered that circNRCAM could competitively bind to ALKBH5, which restrained miR-506-3p expression and promoted NRCAM expression. CONCLUSION: In summary, circNRCAM could up-regulate NRCAM by down-regulating miR-506-3p, thereby enhancing the biological behaviors of PTC cells.

[Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study].

Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.

[The accuracy and feasibility study of freehand pedicle screw insertion for subaxial cervical spine assisted with safe core-referred technique].

Objectives: To construct the "safe core" of the pedicle screw trajectory using CT imaging data of the subaxial cervical spine in adults, and to assess the accuracy and feasibility of the pedicle screw insertion assisted with the "safe core-referred technique" for subaxial cervical spine with a cadaver specimen study. Methods: This is an experimental study. From January 2015 to March 2020,60 adults' CT images data of the cervical spine were collected from the database of the First Affiliated Hospital of Gannan Medical University,and were imported into Mimics 20.0 software. Virtual cervical pedicle trajectory and safe core were constructed according to the self-designed "virtual construction method of pedicle in the subaxial cervical spine". The success rate of the construction and the spatial position data of the virtual safe core of was recorded,including the distance between the safe core and the tangent line of the upper and lower outer edge of Luschka's joint on coronal plane,and the distance between the safe core and the posterior edge of the vertebral body on sagittal plane.The 3.5 mm column was used to simulate the pedicle screw placement,using the safe core as the only hub in pedicle screw trajectory.The length of the anterior pedicle screw trajectory,the interval of the abductive angle of the pedicle screw in axial plane, and the projection area of the entry area on periapical radiograph was calculated.In addition,8 adult cervical cadaver specimens were collected for the pedicle screw insertion experiment.The left side group used the "safe core-referred technique" for pedicle screw insertion,while the right side group used the Abumi method for pedicle screw insertion.The accuracy of pedicle screw placement was verified by CT scan.The difference between the accuracy of subjective judgment based on X-ray monitoring of operator and the actual accuracy of pedicle screw insertion verified by CT scan was compared between the two groups.The chi-square test was used to compare the intergroup data. Results: The total success rate of the virtual construction method for the safe core of the subaxial cervical spine was 97.0% (291/300); The distance between the safe core and the tangent line of the upper and lower outer edge of Luschka's joint on coronal plane was (M(IQR)) 0.91 (0.98) mm (range: 0 to 1.85 mm);The distance between the safe core and the posterior wall on the sagittal plane of the vertebral body was (2.01±0.86) mm (range: 0.67 to 3.53 mm). The distance (anterior pedicle screw trajectory) from the posterior cortex to the central point of the safe core was (11.58±1.00)mm (range: 8.27 to 14.93 mm).The projection area of the entry point on the coronal plane was (36.18±11.67) mm2 (range: 13.38 to 83.11 mm2). Pedicle screw insertion experiment in cervical cadaver specimen showed the rate of intraoperative correction of the pedicle screw trajectory was 7.5% (3/40) in the experimental group and 12.5% (5/40) in the control group (χ2=0.139,P=0.709). The operator 's correct rate of subjective judgment on CT in the stage of pedicle screw trajectory preparation was 100% (40/40) in the experimental group and 82.5% (33/40) in the control group, the difference was statistically significant (χ2=5.638,P=0.018). The actual correct rate of CT verification in the stage of pedicle screw insertion was 100% (40/40) in the experimental group and 90.0% (36/40) in the control group, the difference was statistically significant (χ2=2.368,P=0.124); The operator 's correct rate of subjective judgment in the stage of pedicle screw insertion completion was 100% (83/83) in the experimental group and 92.9% (79/85) in the control group (χ2=4.199,P=0.040). Conclusions: The virtual safe-core of subaxial cervical spine can be use as a reliable anatomical fluoroscopy landmark for freehand pedicle screw insertion."Safe core-referred technique" can improve the accuracy rate of the operator's subjective judgment on the intraoperative fluoroscopy monitoring,and hence improve the accuracy of freehand pedicle screw insertion technology for subaxial cervical spine. And it still needs to be further verified in clinical practice.

Machine-learning-based performance comparison of two-dimensional (2D) and three-dimensional (3D) CT radiomics features for intracerebral haemorrhage expansion.

AIM: To investigate the value of non-contrast CT (NCCT)-based two-dimensional (2D) radiomics features in predicting haematoma expansion (HE) after spontaneous intracerebral haemorrhage (ICH) and compare its predictive ability with the three-dimensional (3D) signature. MATERIALS AND METHODS: Three hundred and seven ICH patients who received baseline NCCT within 6 h of ictus from two stroke centres were analysed retrospectively. 2D and 3D radiomics features were extracted in the manner of one-to-one correspondence. The 2D and 3D models were generated by four different machine-learning algorithms (regularised L1 logistic regression, decision tree, support vector machine and AdaBoost), and the receiver operating characteristic (ROC) curve was used to compare their predictive performance. A robustness analysis was performed according to baseline haematoma volume. RESULTS: Each feature type of 2D and 3D modalities used for subsequent analyses had excellent consistency (mean ICC >0.9). Among the different machine-learning algorithms, pairwise comparison showed no significant difference in both the training (mean area under the ROC curve [AUC] 0.858 versus 0.802, all p>0.05) and validation datasets (mean AUC 0.725 versus 0.678, all p>0.05), and the 10-fold cross-validation evaluation yielded similar results. The AUCs of the 2D and 3D models were comparable either in the binary or tertile volume analysis (all p>0.5). CONCLUSION: NCCT-derived 2D radiomics features exhibited acceptable and similar performance to the 3D features in predicting HE, and this comparability seemed unaffected by initial haematoma volume. The 2D signature may be preferred in future HE-related radiomic works given its compatibility with emergency condition of ICH.

[Safety and effectiveness of interventional bronchoscopy under general anesthesia in the elderly patients with central airway stenosis: a retrospective study].

We retrospectively reviewed the clinical data of patients aged 65 years and older with central airway stenosis who underwent therapeutic bronchoscopy under general anesthesia in Beijing Tiantan Hospital from January 2012 to September 2022. A total of 167 patients were included in the study. One or more comorbidities were present in 151 patients. The number of operation procedure was 230 times. Laryngeal mask ventilation under general anesthesia and electrotomy was the most common method of airway management and operation. The incidence of major complications was 5.2%. One patient with granular cell tumor died of major bleeding during stent removal. The primary malignant lesion, number of comorbidities, electrolyte disturbances and rigid bronchoscopy were risk factors for major complications, and the difference was statistically significant. The overall response rate was 99.4%. The airway stenosis grade, dyspnea score and KPS value were improved, and the differences were statistically significant. Interventional bronchoscopy under general anesthesia appeared to be safe and effective in patients aged 65 years and older with central airway stenosis. Age should not be a contraindication to interventional bronchoscopy.

[Comparison between laparoscopic-assisted natural orifice specimen extraction surgery and conventional laparoscopic surgery for left colorectal cancer: 5-year follow-up results of a randomized controlled study].

Objective: To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer. Methods: This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results: Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7-83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively (P=0.455); disease free survival was 90.0% and 83.3%, respectively (P=0.455); overall recurrence rate 6.6% and 10.0%, respectively (P=0.625); and local recurrence rate both were 3.3% (P=0.990), respectively. None of these differences was statistically significant. Conclusions: NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

Effect of PD-L1 Expression for the PD-1/L1 Inhibitors on Non-small Cell Lung Cancer: A Meta-analysis Based on Randomised Controlled Trials.

AIMS: As PD-L1 expression has been proposed as one of the cancer biomarkers for non-small cell lung cancer (NSCLC), the predictive value of tumour proportional score (TPS) in the effect of immunotherapy [programmed death protein-1/ligand 1 (PD-1/L1) inhibitors] for NSCLC is worth exploring further. Here, we aimed to summarise the outcomes of current NSCLC randomised controlled trials (RCTs) and explore the predictive value of TPS in clinical immunotherapy, including immune checkpoint inhibitors (ICIs) with or without chemotherapy. MATERIALS AND METHODS: RCTs published by PubMed, Medline, Embase and Scopus before February 2023 comparing immunotherapy (PD-1/L1 with or without other therapy) versus a control group in advanced or metastatic NSCLC were included to assess the prognosis according to the patients' TPS with 1% and 50% as the thresholds. The primary endpoints were overall survival and progression-free survival. RESULTS: In total, 28 RCTs containing 17 266 participants with advanced or metastatic NSCLC were included in this meta-analysis. Statistical results showed that compared with TPS <1%, ≥1% or within 1-49%, patients with TPS ≥50% benefited more significantly from the immunotherapy. A subgroup analysis showed that when TPS was <1%, ≥1% or within 1-49%, ICIs + chemotherapy had better efficacy than ICIs alone; PD-1 (such as pembrolizumab) inhibitors had better efficacy than PD-L1 inhibitors (such as atezolizumab). CONCLUSION: The efficacy of immunotherapy (PD-1/L1 inhibitors) for advanced or metastatic NSCLC is influenced by TPS.

[Clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated interstitial lung disease].

Objective: To analyze the clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis associated interstitial lung disease (DM-ILD). Methods: The patients with MDA5+DM-ILD who were admitted to Department of Respiratory Medicine, Nanjing Drum Tower Hospital from January 2017 to March 2021 were enrolled. The clinical data and survival information were analyzed retrospectively. Patients were divided into survival group or death group, and rapid progressive ILD (RP-ILD) group or non-rapid progressive ILD group, according to their survival status and clinical progression. Results: A total of 105 patients with anti-MDA5+DM-ILD (median age of onset 54 years) were enrolled, 58% being female (61 cases). The main sub-type of dermatomyositis was amyopathic dermatomyositis (n=74, 70%), followed by dermatomyositis (n=31, 30%). The main extrapulmonary manifestations were skin lesions (n=60, 57.1%), muscle manifestations(n=20, 19%) and arthralgia/arthritis (n=20, 19%). 15.4% of the patients had positive ANA (antibody titer≥1∶320), and 61.9% of the patients had anti-RO-52 kDa antibody. A total of 66 patients (62.8%) developed RP-ILD, and 58 patients (56.3%) died. Lower oxygenation index (OR=0.974, 95%CI:0.954-0.994, P=0.012) and no joint pain (OR=0.032, 95%CI: 0.002-0.663 P=0.026) were independent risk factors for RP-ILD. Cox regression analysis showed that RP-ILD (HR=3.194, 95%CI:1.025-9.954, P=0.045), older than 53 years (HR=3.450, 95%CI: 1.388-8.577, P=0.008), ferritin level more than 1 330.5 ng/ml (HR=3.032, 95%CI 1.208-7.610, P=0.018) and C-reactive protein (CRP) above 16.95 mg/L (HR=2.794, 95%CI:1.102-7.084, P=0.030) were independent predictors of mortality. Conclusions: The clinical manifestations of patients with anti-MDA5+DM-ILD presenting to the respiratory department were heterogeneous, with most being amyopathic dermatomyositis, and both the incidence of RP-ILD and the risk of death were high. Even in the absence of associated rash, joint, or muscle manifestations, anti-MDA5 antibody screening should be considered in patients with rapidly progressive ILD who were negative on baseline autoantibody screening but positive for anti-RO52kDa antibody.

[Inhibitor of growth protein-2 silencing alleviates angiotensin â ¡-induced cardiac remodeling in mice by reducing p53 acetylation].

OBJECTIVE: To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism. METHODS: An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg-1 · min-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits. RESULTS: The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression. CONCLUSION: Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.

[Advances in three-dimensional tumor models for colorectal cancer].

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.