Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

Objective To explore the value of combined ultrasound parameters, including the hepatorenal index (HRI) and renal resistance index (RRI), with cystatin C (CysC) in monitoring early acute kidney injury (AKI) after liver transplantation. Methods Perioperative data from 121 liver transplant recipients who received organs from donation after brain death were collected. The HRI and RRI of the recipients were measured on postoperative days 1-7 and at 1 month, and the CysC levels were measured on postoperative day 1. The recipients were divided into the AKI group (n=53) and the non-AKI group (n=68) based on whether AKI occurred within 7 days after operation. The data of the two groups were compared, and the ultrasound parameters before and after recovery in the AKI group were analyzed. The value of combined HRI, RRI and CysC in monitoring AKI was also analyzed. Results AKI occurred in 53 recipients, with an incidence rate of 43.8%, including 30 cases of stage 1, 18 cases of stage 2, and 5 cases of stage 3. Among them, 49 cases occurred on postoperative day 1, and 4 cases occurred on postoperative day 2. Of these, 43 cases recovered within 7 days after surgery, 8 cases recovered within 2 months after surgery, 1 case was lost to follow-up, and 1 case received renal replacement therapy. The body mass index and preoperative CysC levels were higher in the AKI group than in the non-AKI group, and the operative time was longer in the AKI group than in the non-AKI group (all P < 0.05). The HRI on postoperative day 1 was lower in the AKI group than in the non-AKI group, while the RRI and CysC levels were higher (all P < 0.05). When AKI occurred, the HRI was lower than the baseline level, and the RRI was higher than the baseline level. As AKI recovered, the HRI gradually increased, and the RRI gradually decreased. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of HRI ≤ 1.12 for predicting AKI were 0.623 and 0.878, respectively, with an area under the curve (AUC) of 0.801. The sensitivity and specificity of RRI ≥ 0.65 for predicting AKI were 0.878 and 0.676, respectively, with an AUC of 0.825. The sensitivity and specificity of CysC ≥ 1.38 mg/L for predicting AKI were 0.736 and 0.882, respectively, with an AUC of 0.851 (all P<0.01). The combination of HRI and CysC (AUC=0.897, P<0.01), RRI and CysC (AUC=0.910, P<0.01), and all three parameters combined (AUC=0.934, P<0.01) were more effective than using each parameter alone. Conclusions HRI and RRI may be used to monitor the occurrence and recovery of early AKI after liver transplantation. The combination of these two parameters with CysC has a high application value in monitoring early AKI after liver transplantation.

Objective:Farfarae Flos has the effect of cough suppression and phlegm elimination,with cough suppression as the main function.Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect,and some components have been confirmed to have cough suppressant activity.However,the antitussive material basis of Farfarae Flos has not been systematically elucidated.This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography(HPLC)fingerprint of Farfarae Flos extract with its cough suppressant activity. Methods:HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data.Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract.SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups,a positive control group,and a blank control group(12 groups in total),with 10 guinea pigs in each group.The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10(4 g/kg),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days.The guinea pigs were placed in 5 L closed wide-mouth bottles,and 17.5%citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes.The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig.Grey relational analysis(GRA)and partial least squares regression(PLSR)were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data,and predict the group of active ingredients in Farfarae Flos with antitussive activity.The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity:SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group,an active ingredient group,a positive control group,and a blank control group(4 groups in total),with 10 guinea pigs in each group.The S9 group was administered Farfarae Flos extract S9(4 g/kg),the active ingredient group was administered the predicted combination of antitussive active ingredients(dose equivalent to 4 g/kg of Farfarae Flos extract S9),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days,and animal modeling and observation of efficacy indicators were the same as above. Results:The HPLC fingerprint of 10 batches of Farfarae Flos extract was established,and the peak area data of 14 main common peaks were obtained.The antitussive effect data of 10 batches of Farfarae Flos extract were obtained.Compared with the blank control group,the cough latence in the positive control group and S1,S2,S3,S4,S6,S7,S8,S9,S10 groups was prolonged(all P<0.01),while the cough frequency in 5 minutes in the positive control group and S1,S2,S4,S6,S8,S9,S10 groups was decreased(all P<0.05).The analysis of spectrum-effect relationship revealed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercitrin,and rutin had high contribution to the antitussive effect of Farfarae Flos,and the 6 components were predicted to be the antitussive component group of Farfarae Flos.The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05),which confirmed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercetin,and rutin were the antitussive component group of Farfarae Flos. Conclusion:The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos.The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Objective To observe the value of long TR three-dimensional inversion recovery sequence with real reconstruction(3D real IR)for quantifying inner ear endolymphatic hydrops(EH).Methods Totally 46 Ménière's disease(MD)patients and 21 healthy volunteers were prospectively enrolled.MR scanning for inner ear based on 3D real IR and 3D fluid attenuated inversion recovery(3D FLAIR)sequence 4-6 h after administration of contrast agents were performed.The imaging qualities were scored and compared between groups.The endolymphatic space area and the membranous labyrinth area of cochlea and vestibule,as well as endolymph/membranous labyrinth area percentage were calculated,the present or not of EH and the grade of EH were evaluated.EH inner ears of MD patients were enrolled in EH group,while inner ears of healthy volunteers were taken as controls(control group).The endolymphatic space area,membranous labyrinth area and endolymph/membranous labyrinth area percentage of cochlea and vestibule were compared between groups.The receiver operating characteristic(ROC)curve was drawn to calculate the diagnostic efficacy of the above indexes.Results Cochlear and/or vestibular EH were detected in 56 ears,including cochlear EH in 52 ears and vestibular EH in 45 ears among 46 MD patients(EH group),but not in 42 ears in control group.The subjective quality scores of 3D real IR images were higher than those of 3D-FLAIR(both P＜0.05).Quantitative analysis based on 3D real IR images revealed that,compared with control group,significantly larger endolymph areas and endolymph/membranous labyrinth area percentages in both cochlea and vestibule were found in EH group(all P＜0.001).The area under the curve(AUC)of cochlear or vestibular endolymph/membranous labyrinth area percentage for identifying inner ear EH was 0.999 and 0.985,respectively.Taken 13.64％and 24.13％as the critical value of cochlear or vestibular endolymph,the specificity was 100％and 92.86％,respectively,and the sensitivity was 96.43％and 96.43％,respectively.Conclusion MR long TR 3D real IR was helpful to quantifying inner ear EH.

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.
Humans ; Immune Checkpoint Inhibitors ; Neoplasm Recurrence, Local ; Lung Neoplasms/genetics* ; Thoracic Neoplasms/pathology* ; Adenocarcinoma ; DNA Helicases ; Nuclear Proteins ; Transcription Factors

Objective:To investigate the clinicopathological characteristics and possible pathogenesis of immune checkpoint inhibitor (ICI) induced myocarditis, and to improve understanding of this new type of myocarditis.Methods:Two cases of ICI induced myocarditis with endomyocardial biopsy available for review were selected from the cases with immune-related adverse events treated by ICI in Peking University First Hospital, Beijing, China from 2020 to 2022. The clinical data, histomorphological characteristics, PD-L1 expression of cardiomyocytes, and classification of inflammatory cells in two cases of ICI-induced myocarditis were analyzed. Relevant literature was reviewed.Results:Case 1 was a 64-year-old male diagnosed with gastric signet ring cell carcinoma. Case 2 was a 56-year-old male ad diagnosed with lung squamous cell carcinoma. Both patients developed acute myocarditis during PD-1 inhibitor treatment, and the disease progressed rapidly. Case 2 was more serious than case 1. Endomyocardial biopsy showed definite cardiomyocytic injury and prominent inflammatory infiltration in both cases, which met the full Dallas criteria for myocarditis. The degenerated and necrotic cardiomyocytes accounted for about 10% of the tissues in case 1 and 30% in case 2, respectively. In case 1, the inflammatory cells counted in the densest area were about 150/HPF, comprised of CD20 + cells (about 5/HPF), CD3 + cells (about 60/HPF), CD8 + cells (about 50/HPF) and CD68 + cells (about 70/HPF). In case 2, the inflammatory cells counted in the densest area were about 350/HPF, comprised of CD20 + cells (0/HPF), CD3 + cells (about 100/HPF), CD8 + cells (about 90/HPF) and CD68 + cells (about 200/HPF). In both cases, PD-L1 + cardiomyocytes aggregated in the inflammatory lesions, and the percentage was about 8% and 30% in case 1 and case 2, respectively. Conclusions:ICI-induced myocarditis is frequently acute onset, severe symptoms, and rapid progression. The histological morphology meets the full Dallas criteria for myocarditis. Expression of PD-L1 in cardiomyocytes can be detected in the inflammatory lesions. The inflammatory cells are comprised of CD8 + T lymphocytes and macrophages and the number of macrophages significantly exceeds that of lymphocytes. Combined with the pathological characteristics and the history of ICI treatment, the diagnosis of ICI-induced myocarditis can be made.

UPLC-Q-TOF-MS combined with network pharmacology and experimental verification was used to explore the mechanism of acupoint sticking therapy(AST) in the intervention of bronchial asthma(BA). The chemical components of Sinapis Semen, Cory-dalis Rhizoma, Kansui Radix, Asari Radix et Rhizoma, and Zingiberis Rhizoma Recens were retrieved from TCMSP as self-built database. The active components in AST drugs were analyzed by UPLC-Q-TOF-MS, and the targets were screened out in TCMSP and Swiss-TargetPrediction. Targets of BA were collected from GeneCards, and the intersection of active components and targets was obtained by Venny 2.1.0. The potential targets were imported into STRING and DAVID for PPI, GO, and KEGG analyses. The asthma model induced by house dust mite(HDM) was established in mice. The mechanism of AST on asthmatic mice was explored by pulmonary function, Western blot, and flow cytometry. The results indicated that 54 active components were obtained by UPLC-Q-TOF-MS and 162 potential targets were obtained from the intersection. The first 53 targets were selected as key targets. PPI, GO, and KEGG analyses showed that AST presumedly acted on SRC, PIK3 CA, and other targets through active components such as sinoacutine, sinapic acid, dihydrocapsaicin, and 6-gingerol and regulated PI3 K-AKT, ErbB, chemokine, sphingolipid, and other signaling pathways to intervene in the pathological mechanism of BA. AST can improve lung function, down-regulate the expression of PI3 K and p-AKT proteins in lung tissues, enhance the expression of PETN protein, and reduce the level of type Ⅱ innate immune cells(ILC2 s) in lung tissues of asthmatic mice. In conclusion, AST may inhibit ILC2 s by down-regulating the PI3 K-AKT pathway to relieve asthmatic airway inflammation and reduce airway hyperresponsiveness.
Acupuncture Points ; Animals ; Asthma/drug therapy* ; Drugs, Chinese Herbal ; Immunity, Innate ; Lymphocytes ; Mice ; Network Pharmacology

OBJECTIVE: To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C₃-C₇) in order to provide a finite element modeling method for anterior cervical reconstruction. METHODS: The CT data of the cervical segment (C₁-T₁) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C₃-C₇) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C₅ and C₆ vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C₃ in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups. RESULTS: There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C₃-C₇) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C_3,4 segment was increased slightly. CONCLUSION The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.
Adult ; Biomechanical Phenomena ; Bone Screws ; Cervical Vertebrae/surgery* ; Finite Element Analysis ; Humans ; Male ; Range of Motion, Articular ; Spinal Fusion

Interaction exists in lung cancer and microbiota. Lung microecological homeostasis can improve the immune tolerance, enhance immune suppression, and inhibit inflammatory responses, to reduce the lung cancer; while lung cancer can lead to pulmonary microecological imbalance, change the lung environment, and promote tumor cell proliferation. Therefore, modulating microbial flora and microecological immunotherapy may be a potential and preventive treatment for lung cancer, to restore tumor immunosuppression and improve patient survival. However, the individual differences in the lung microecology, because of different genetics, ethnic characteristics, and dietary habits, increasing the difficulty of precise diagnosis and treatment, which is also the current bottleneck in the application of microecological immunotherapy. Otherwise, the effectiveness of regulatory measures such as probiotics, prebiotics or antimicrobials is questionable. The research on microbial flora is still in its infancy, and further exploration is needed to form a standardized, effective, and precise treatment plan. So, standardized, effective, and precise microbial flora treatment strategies need to be further explored.
Humans ; Probiotics ; Prebiotics ; Microbiota ; Lung Neoplasms