BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder （CID）. Default mode network （DMN） dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However， it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity （EC） of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam， so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder， third edition （ICSD-3） were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference， patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group （n=52） or the estazolam group （n=30）. Ultimately， 66 patients completed follow-up assessments （modified Suanzaoren Decoction group， n=41； estazolam group， n=25）. All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex （mPFC）， bilateral inferior parietal lobule （IPL）， and precuneus （PCUN） were selected as seed regions. Granger causality analysis （GCA） was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline， significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus （t=5.24， Z=4.84， voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）， with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions （P>0.05）. Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically， EC from the left IPL to the supplementary motor area （SMA） decreased after treatment （modified Suanzaoren Decoction group： t=-6.28， Z=5.208； estazolam group： t=-5.58， Z=4.425）. Conversely， EC from the SMA to the left IPL increased （modified Suanzaoren Decoction group： t=5.89， Z=4.968； estazolam group： t=6.15， Z=4.720）. Furthermore， both groups demonstrated reduced EC from the PCUN to the left IPL （modified Suanzaoren Decoction group： t=-5.85， Z=4.94； estazolam group： t=-5.75， Z=4.515）， and elevated EC from the left IPL to the PCUN （modified Suanzaoren Decoction group： t=5.29， Z=4.579； estazolam group： t=4.55， Z=3.826） （voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）. No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group （P>0.05）. ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome， both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. ［Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region （number， 2019MS08099）； ClinicalTrials.gov number， NCT06452953］

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVES: To evaluate the short-term clinical efficacy of transcatheter edge-to-edge repair (TEER) in patients with moderate to severe mitral regurgitation. METHODS: Clinical data of patients with moderate to severe mitral regurgitation who underwent TEER in the Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University from April 2021 to May 2024, were retrospectively analyzed, including preoperative baseline clinical and echocardiography data, intraoperative data and 6-month postoperative follow-up data. RESULTS: A total of 67 patients' (47 males and 20 females) data were included, of whom 62 completed 6-month follow-up. The immediately postoperative success rate was 88.1% (59/67), and 83.9% (52/62) patients exhibited mitral regurgitation ≤2+ at 6 months postoperatively, showing significant improvement compared with preoperative (P<0.05). The proportion of patients with mitral regurgitation ≤2+ at 6 months was significantly higher in the degenerative mitral regurgitation (DMR) group than that in the functional mitral regurgitation (FMR) group (P<0.05). The mean mitral valve gradient (MVG) in DMR group was increased from (3.1±1.2) mmHg (1 mmHg=0.133 kPa) to (3.7±1.2) mmHg 6 months after operation (P<0.05), while there was no significant change in FMR group (P>0.05). Compared with those before operation, the N-terminal pro-B-type natriuretic peptide levels in both FMR and DMR groups were significantly lower at 6 months postoperatively (all P<0.05), and the left atrial volume index and left atrial anteroposterior diameter were also significantly lower (all P<0.05). The left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly reduced 6 months after operation in the FMR group (all P<0.05), but no significant changes were observed in the DMR group (all P>0.05). The ejection fraction was not significantly changed before and after operation in both groups (all P>0.05). The mitral regurgitation, tricuspid regurgitant, and pulmonary artery pressure were significantly reduced in both groups at 6 months postoperatively (all P<0.05). CONCLUSIONS TEER is effective for moderate to severe mitral regurgitation. The improve-ments in left ventricular remodeling are more pronounced in patients with FMR while the degree of mitral regurgitation is more significant in DMR patients. However, MVG elevation is more common during the follow-up.
Humans ; Mitral Valve Insufficiency/surgery* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Treatment Outcome ; Mitral Valve/surgery* ; Cardiac Catheterization/methods* ; Heart Valve Prosthesis Implantation/methods* ; Adult ; Follow-Up Studies

In recent years, as a new omics field, metabolomics has been proved to be of great value in the study of the mechanism of occurrence and progression, the screening of new biomarkers and the development of novel therapeutic strategies in many diseases including tumors. In this review, we briefly summarized the research methods and techniques of metabolomics, and focused on the latest research progress of metabolomics in the pathogenesis of hematological malignancies represented by leukemia, lymphoma and multiple myeloma, screening of biomarkers for diagnosis and prognosis, and development of new therapeutic strategies. This article proposes the limitations of metabolomics and future research strategies, and provides a new exploration direction for accurate diagnosis and treatment as well as prognosis evaluation of hematological malignancies.
Humans ; Metabolomics/methods* ; Hematologic Neoplasms/diagnosis* ; Biomarkers, Tumor

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective:To compare the efficacy of 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-octreotide (OC) PET/CT and MRI in detecting liver metastases (LM) of neuroendocrine neoplasm (NENLM). Methods:18F-AlF-NOTA-OC PET/CT and MRI findings (dynamic contrast enhanced MRI and diffusion weighted imaging) of 44 patients (26 males, 18 females, age (53.8±13.4) years) with neuroendocrine neoplasm (NEN) confirmed by pathological or clinical follow-up in the First Affiliated Hospital of Zhengzhou University from July 2021 to December 2023 were retrospectively analyzed. According to the size of LM, patients were divided into 3 groups with long diameter ≤1 cm, 1 cm< long diameter ≤2 cm and long diameter >2 cm. According to the 2019 WHO pathological grade, patients were divided into G1, G2, G3 and neuroendocrine carcinoma groups. McNemar χ2 test was used to compare the difference in detecting LM and lesions between the two methods. Results:The detection rate of 18F-AlF-NOTA-OC PET/CT and MRI in patients with NENLM was 95.45%(42/44). Among 44 patients, 227 lesions were detected by PET/CT and 303 were detected by MRI. Based on lesion analysis ( n=307), the detection rate of 18F-AlF-NOTA-OC PET/CT for NENLM was lower than that of MRI (73.94%(227/307) vs 98.70%(303/307); χ2=66.96, P<0.001). For NENLM with long diameter ≤1 cm, 1 cm < long diameter ≤2 cm, long diameter >2 cm, the detection rates of MRI were higher than those of 18F-AlF-NOTA-OC PET/CT (98.72%(77/78), 93.55%(116/124), 97.35%(110/113) vs 47.44%(37/78), 73.39%(91/124), 87.61%(99/113); χ2 values: 5.88-36.21, all P<0.05). Conclusions:Compared with 18F-AlF-NOTA-OC PET/CT, MRI has a higher detection rate for NENLM with different long diameters of NEN, especially for lesions with long diameter≤1 cm.

Objective:To investigate the clinical and pathological characteristics of primary thoracic synovial sarcoma (PTSS).Methods:Forty-two PTSS cases diagnosed at the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from October 2011 to April 2024 were analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. Their clinicopathological features were also reviewed. SS18 rearrangement was assessed in 28 cases using fluorescence in situ hybridization (FISH). Next generation sequencing (NGS) was performed on 8 cases.Results:Among the 42 cases, there were 23 biopsies and 19 surgically-removed specimens. One case was a specimen resected after neoadjuvant chemotherapy. There were 22 males and 20 females, with an age ranging from 6 to 68 years. Twenty-nine cases occured in the lung, 6 in mediastinum, 4 in pericardium, 1 in visceral pleura, and 1 in right atrium. One case did not show any unequivocal primary site. Computed tomography showed the tumors were manifested as a cystic mass, a solid mass, or thickening of the pleura and pericardium. Thirty-two cases had respiratory symptoms, while 19 had pleural effusion. One case had a history of radiotherapy for papillary thyroid carcinoma. Nineteen patients were treated with surgery, while 19 were treated with chemotherapy without surgery. Four patients were diagnosed and discharged, without specific treatment on the record. Morphologically, 1 case was biphasic type, 39 cases were monophasic type, and 2 cases were poorly differentiated type. In addition to the typical morphology of synovial sarcoma, tumors also showed pulmonary bullous changes, stromal collagen hyalinization, hemangiopericytoma-like vasculature, stromal edematous myxoid changes, and microcystic structure. Immunohistochemically, all cases were diffusely positive for TRPS1 (22/22), TLE1 (21/22), CD99 (26/26), SS18-SSX (25/25) and INI1 (12/12), including 3 cases with decreased expression of INI1. Twenty-one cases were focally positive for EMA (21/30), 4 cases for SMA (4/23), 2 cases for S-100 (2/28), and 2 cases (2/35) for CKpan. Twenty-eight cases (28/28) had SS18 rearrangement displaying a split signal on FISH analysis. Eight cases were found to have mutations in SMC1A, NOTCH2, CDK12, SPRY4, BRCA1, STK11, NF2, and PDGFRα genes using NGS. Eighteen of the 29 patients survived and 16 showed disease progression.Conclusions:PTSS is more commonly found in the lungs than other sites and has non-classical morphological features of various types, which need to be differentiated from other tumors. TRPS1 is highly expressed in PTSS and has certain diagnostic values. The diagnosis of PTSS also requires combination of patient′s medical history with thorough imaging studies.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.