Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective To observe the effect of neuromuscular electrical stimulation(NMES)on interleukin-6(IL-6)/STAT3 signaling pathway in mice after spinal cord injury,and to explore the mechanism of its effect on motor function recovery.Methods Seventy-two SPF grade mice were randomly divided into sham operation group,spinal cord injury(SCI)group and NMES group.BMS score,inclined plane test and neuromuscular electrophysiology(EMG)were used to evaluate the recovery of spinal cord injury in mice.Western blotting and Real-time PCR were used to detect the expression of inflammatory factors,IL-6/STAT3,glial fibrillary acidic protein(GFAP)and brain-derived neurotrophic factor(BDNF)in spinal cord tissues of three groups of mice.HE staining was used to observe the pathological changes of spinal cord injury.Results BMS scores and the inclined plane test of mice in the NMES group were higher than those in SCI group(P＜0.05).The maximum amplitude of motor evoked potential in NMES group was higher than that in SCI group(P＜0.05).The expressions of TNF-α,IL-12A and GFAP in the spinal cord of NMES group were lower than that of SCI group(P＜0.05),while the expressions of TGF-β,IL-10 and BDNF were higher than that of SCI group(P＜0.05).The protein expressions of IL-6/STAT3 signaling pathway of NMES group were lower than that of SCI group(P＜0.05).Conclusion Neuromuscular electrical stimulation plays an anti-inflammatory role by inhibiting the IL-6/STAT3 signaling pathway,thereby promoting the recovery of hind limb motor function in mice after spinal cord injury.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective: To investigate the spontaneous nystagmus (SN) and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis (VN). Methods: This is a cross-sectional study. A total of 61 patients with VN admitted to the Department of Neurology of Shanxi Bethune Hospital from June 2020 to October 2021, 39 were male and 22 were female, with a mean age of (46±13) years old and male to female ratio of 1.77∶1. According to SN characteristics, 61 patients were divided into non-nystagmus group(nSN), horizontal nystagmus group(hSN) and horizontal-torsional nystagmus group (htSN). Clinical data were collected, and SN, unilateral weakness (UW), directional preponderance (DP), and video head impulse test (vHIT) gain were used as observation indicators. Statistical analysis by SPSS23.0 software. Normal distributed quantitative data (age, semicircular canal gain, SN intensity) were expressed by x¯±s, non-normal distributed quantitative data (disease course, UW, DP) were expressed by M(Q₁,Q₃), qualitative data were expressed by rate and composition ratio, difference analysis by one-way ANOVA, rank sum test, Chi-square test or Fisher's exact probability method, considered by P value<0.05. Results: (1)The disease course of nSN, hSN and htSN was 7.0 (4.0, 12.5), 6.0 (3.5, 11.5), and 3.0 (2.0, 6.5) days respectively, and there were statistical differences (χ2=7.31,P=0.026).(2)The horizontal nystagmus intensity of htSN was (16.8±8.6)°/s, which was significantly higher than that of (9.8±4.7)°/s in hSN (t=3.71, P<0.001). There was no significant difference in the positive rate of UW between the three groups (P=0.690), and there was a significant difference in the positive rate of DP in the three groups (χ2=12.23, P=0.002). The horizontal nystagmor intensity in the htSN was positively correlated with the vertical nystagmus intensity (r=0.59, P=0.001).(3)The gain of the affected horizontal canal of the three groups was statistically different (F=8.28, P=0.001), and the gain of the horizontal canal of hSN and htSN was significantly lower than that of nSN (t=2.74, P=0.008; t=4.05, P<0.001); The gain of the affected anterior canal in the three groups was statistically different (F=5.32, P=0.008). The gain of the anterior canal in both nSN and hSN was significantly higher than that in htSN (t=3.09, P=0.003; t=2.15, P=0.036). The horizontal canal gain of htSN is positively correlated with the anterior canal gain (r=0.74, P<0.001).(4)The affected semicircular canals in the two groups with no-vertical-component nystagmus (nSN and hSN) and the htSN were counted. The composition ratio of the affected semicircular canals in the two groups was different (χ2=8.34, P=0.015). Conclusion: The occurrence of SN in patients with VN is related to many factors, such as the disease course, low and high frequencies, and the severity of the condition in the affected semicircular canal.
Humans ; Male ; Female ; Adult ; Middle Aged ; Vestibular Neuronitis ; Cross-Sectional Studies ; Semicircular Canals ; Nystagmus, Pathologic ; Head Impulse Test ; Disease Progression

In this paper, the clinical data of a case of accidental poisoning of dimethylformamide in a traffic accident was analyzed. The patient was trapped in the driving room, his limbs were soaked in dimethylformamide for a long time, and dimethylformamide was inhaled at the same time. After 4 days of treatment in a local hospital, he was transferred to the Department of Poisoning & Occupational Diseases, Emergency Medicine of Qilu Hospital of Shandong University for treatment. The main clinical manifestation of the patient was liver damage and intractable abdominal pain, which was cured by active treatment.
Male ; Humans ; Dimethylformamide ; Abdominal Pain ; Occupational Diseases/complications* ; Poisoning

OBJECTIVE: To investigate the surgical strategy for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. METHODS: The clinical data of 16 patients with large and giant recurrent meningioma in the middle and posterior third part of the superior sagittal sinus with extracranial invasion who underwent surgery in the Department of Neurosurgery of Peking University Third Hospital from May 2019 to May 2022 were retrospectively analyzed. All the patients underwent brain-enhanced magnetic resonance imaging (MRI), magnetic resonance venography (MRV), computed tomography angiography (CTA) and three-dimensional skull computed tomography (CT) before, to evaluate the extent of tumor invasion, the edema of brain tissue, the degree of skull damage, the blood supply of the tumor, and the degree of compression of the superior sagittal sinus, etc, and to formulate an individualized surgical plan. The neurological function of the patients was evaluated 1 week, 1 month, and 3 months after the operation, and the tumor condition was evaluated by brain-enhanced MRI 3 months, 6 months, and 1 year after the operation. RESULTS: The tumors in the 16 patients were all located in the middle and posterior 1/3 part of the superior sagittal sinus and invaded extracranially. Among them, 8 cases were operated for the second time, 6 cases for the third time, and 2 cases for the fourth time; In the last operation, the bone flap was used to repair the skull in 4 cases, and the titanium mesh was used in 12 cases; Tumor arterials of 3 cases were embolized under digital subtraction angiography (DSA). Tumors of 10 cases were resected at Simpson grade Ⅰ, and 6 cases at Simpson grade Ⅱ; 2 cases underwent decompressive craniectomy during operation, and 14 cases underwent cranioplasty at the same time; scalp incisions of 14 cases were directly sutured, and flap transposition was used in 14 cases. When evaluating nerve function after operation, the limb muscle strength was improved compared with that before operation, and the Karnofsky performance scale (KPS) score reached 100 points 3 months after operation. During the follow-up, 1 patient's tumor recurred after 1 year and received Gamma Knife treatment, and the rest of the patients had no recurrence during the follow-up period. CONCLUSION Surgical treatment is the first choice for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. It is a safe and effective surgical method to take individualized surgical plan after detailed preoperative assessment of cerebral edema, tumor blood supply, venous sinus compression, and scalp invasion.
Humans ; Meningeal Neoplasms/surgery* ; Meningioma/surgery* ; Neoplasm Recurrence, Local/surgery* ; Retrospective Studies ; Superior Sagittal Sinus/surgery* ; Titanium

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Purpose: The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. Materials and Methods: Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. Results: Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). Conclusion This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.