Methods: Motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were recorded in 48 patients with TOLF (hybrid 20 vs. en bloc 28) during surgery. Patients were categorized based on MEP/SEP improvement, deterioration, or no change, and MEP/SEP improvement rates were measured in the improvement group. Furthermore, all patients were assessed using the Ashworth and modified Japanese Orthopedic Association scores. Results: The incidences of both MEP/SEP improvement (21.4% vs. 25.0%, p=0.772) and deterioration (21.4% vs. 20.0%, p=0.904) were similar between the en bloc and hybrid laminectomy groups, and no difference in preoperative and postoperative clinical assessments was observed between the two groups (p>0.05). In four patients (4/28, 14.3%) undergoing en bloc laminectomy, MEP amplitudes initially increased after OLF removal but gradually decreased. This delayed MEP reduction did not occur in the hybrid laminectomy group. Furthermore, more patients undergoing en bloc laminectomy had CFL than those undergoing hybrid laminectomy (46.4% vs. 15.0%, p=0.023). In the improvement group, the hybrid laminectomy group exhibited higher MEP improvement rates in the bilateral abductor hallucis than the en bloc laminectomy group (left side: 213.4%±35.9% vs. 152.5%±41.0%, p=0.028; right side: 201.2%±32.0% vs. 145.2%±46.3%, p=0.043). Conclusions Compared with en bloc laminectomy, hybrid laminectomy may be a safe and effective method for treating multilevel TOLF, potentially reducing intraoperative spinal cord irritation and CFL and causing relatively better functional recovery.

Methods: Motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were recorded in 48 patients with TOLF (hybrid 20 vs. en bloc 28) during surgery. Patients were categorized based on MEP/SEP improvement, deterioration, or no change, and MEP/SEP improvement rates were measured in the improvement group. Furthermore, all patients were assessed using the Ashworth and modified Japanese Orthopedic Association scores. Results: The incidences of both MEP/SEP improvement (21.4% vs. 25.0%, p=0.772) and deterioration (21.4% vs. 20.0%, p=0.904) were similar between the en bloc and hybrid laminectomy groups, and no difference in preoperative and postoperative clinical assessments was observed between the two groups (p>0.05). In four patients (4/28, 14.3%) undergoing en bloc laminectomy, MEP amplitudes initially increased after OLF removal but gradually decreased. This delayed MEP reduction did not occur in the hybrid laminectomy group. Furthermore, more patients undergoing en bloc laminectomy had CFL than those undergoing hybrid laminectomy (46.4% vs. 15.0%, p=0.023). In the improvement group, the hybrid laminectomy group exhibited higher MEP improvement rates in the bilateral abductor hallucis than the en bloc laminectomy group (left side: 213.4%±35.9% vs. 152.5%±41.0%, p=0.028; right side: 201.2%±32.0% vs. 145.2%±46.3%, p=0.043). Conclusions Compared with en bloc laminectomy, hybrid laminectomy may be a safe and effective method for treating multilevel TOLF, potentially reducing intraoperative spinal cord irritation and CFL and causing relatively better functional recovery.

Methods: Motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were recorded in 48 patients with TOLF (hybrid 20 vs. en bloc 28) during surgery. Patients were categorized based on MEP/SEP improvement, deterioration, or no change, and MEP/SEP improvement rates were measured in the improvement group. Furthermore, all patients were assessed using the Ashworth and modified Japanese Orthopedic Association scores. Results: The incidences of both MEP/SEP improvement (21.4% vs. 25.0%, p=0.772) and deterioration (21.4% vs. 20.0%, p=0.904) were similar between the en bloc and hybrid laminectomy groups, and no difference in preoperative and postoperative clinical assessments was observed between the two groups (p>0.05). In four patients (4/28, 14.3%) undergoing en bloc laminectomy, MEP amplitudes initially increased after OLF removal but gradually decreased. This delayed MEP reduction did not occur in the hybrid laminectomy group. Furthermore, more patients undergoing en bloc laminectomy had CFL than those undergoing hybrid laminectomy (46.4% vs. 15.0%, p=0.023). In the improvement group, the hybrid laminectomy group exhibited higher MEP improvement rates in the bilateral abductor hallucis than the en bloc laminectomy group (left side: 213.4%±35.9% vs. 152.5%±41.0%, p=0.028; right side: 201.2%±32.0% vs. 145.2%±46.3%, p=0.043). Conclusions Compared with en bloc laminectomy, hybrid laminectomy may be a safe and effective method for treating multilevel TOLF, potentially reducing intraoperative spinal cord irritation and CFL and causing relatively better functional recovery.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective:To explore the clinical application value of a deep learning algorithm-based ultrasound biomicroscopy (UBM) image analysis system for primary angles-closure glaucoma (PACG) anterior located ciliary body.Methods:A diagnostic test study was conducted.A total of 2 132 UBM images from 726 eyes of 378 PACG patients who underwent UBM examination were collected at Renmin Hospital of Wuhan University from August 2022 to December 2023.The dataset was divided into a training set of 1 599 images and a test set of 533 images, and a deep learning algorithm was employed to construct a model.An additional 334 UBM images from 101 eyes of 69 PACG patients treated at Huangshi Aier Eye Hospital were selected to conduct external testing.A separate set of another 110 UBM images were selected for a human-machine competition to compare the accuracy and speed between anterior located ciliary body evaluation system and three senior ophthalmologists.Furthermore, eight junior ophthalmologists assessed the 110 UBM images independently without and with the assistance of the model, and the differences between the two evaluations were analyzed to assess the assisstance effect of the model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109).Results:The model achieved an accuracy of 93.43% for anterior located ciliary body identification in the internal test set, with a sensitivity of 84.30% and a specificity of 97.78%.The model also performed well on the external test set with an accuracy of 92.81%.In the human-machine competition, the model's accuracy was comparable to that of the senior ophthalmologists and outperformed two of the three senior ophthalmologists.The average total time of the three senior ophthalmologists was 726.73 seconds, approximately 12.47 times longer than the model's 58.30 seconds.With model assistance, the diagnostic accuracy of the eight junior ophthalmologists was 86.71%, which was significantly higher than 76.25% without model assistance ( χ2=-7.550, P<0.001).And the image evaluation time was (714.91±213.82)seconds, which was significantly lower than (987.90±238.56)seconds without model assistance ( t=2.774, P<0.05). Conclusions:The UBM image analysis system based on a deep learning algorithm demonstrates high accuracy in diagnosing anterior located ciliary body in PACG and provides a strong support for the UBM image recognition training of junior ophthalmologists.

Objective To explore the modal testing method for the three-axis manned centrifuge under elastic boundary conditions with considerations on its complicated structure and high rotational inertia.Methods Modal testing was carried out with a three-axis manned centrifuge under elastic boundary conditions as the subject and a force hammer as the excitation source according to GJB 2706A-2008 Modal tests method for spacecraft and GB/T 11349.3-1992 Experimental determination of mechnical mobility measurements using impact excitation.Four times of hammering were carried out at each excitation position,and the data of the four times of hammering underwent linear average computation.Data acquisition was implemented with a three-axis accelerometer and a 64-channel data collector,and the modal data were analyzed using a frequency response function based on the Test.Lab modal test and analysis software.Results The coherence coefficient of the excitation signal was not lower than 0.8 in the 30 Hz band;the first three orders of the system's intrinsic vibrations were all torsional vibrations,with the frequencies of 9.15,15.66 and 19.22 Hz,respectively;the first order frequency of the system was about 9.15 Hz for both Z18 and Z21 excitation positions,and each of the second and third order frequencies similar situations were observed for also had a roughly equal value for the two excitation positions.Conclusion The force hammer testing method is applicable for the modal testing of the three-axis manned centrifuge,ensuring equipment safety and subject comfort.Referen-ces are provided for the following structural optimization design.[Chinese Medical Equipment Journal,2024,45(8):38-43]

Objective To explore the correlation between lung injury and human neutrophil lipocalin(HNL)in rats with sepsis.Methods 45 rats were randomly divided into a control group,a sham group,and a model group.The model group was to construct a rat sepsis lung injury model,the sham group was to free cecum laparotomy and then close abdomen without ligation and puncture,and the control group was with healthy rats.Serum interleukin(IL)-6,IL-1β,tumor necrosis factor-a(TNF-α),and HNL in each group of rats were detected with reagent kit.Oxygenation index was detected by blood gas analysis system.Lung wet/dry(W/D)ratio was calculated.Patho-logical morphology of lung tissue was observed by HE staining,and lung injury score was calculated.Results There were no significant differences in IL-6,IL-1β,TNF-α,HNL levels,oxygenation index,lung tissue wet/dry ratio,and lung injury score between the control group and the sham group at 12,24 and 36 hours(all P＞0.05).Compared with the sham group,IL-6,IL-1β,TNF-α,HNL levels,oxygenation index,lung tissue wet/dry ratio,and lung injury score in the model group increased at 12,24 and 36 hours,with significant differences(all P＜0.05).At 12,24 and 36 hours,lung tissue structure of rats was normal in the control group,with no edema ob-served;there were only a few inflammatory cells in the lung tissue of rats from the sham group;while in the model group,lung tissue structure of rats was severely injured,pulmonary alveoli collapsed,and inflammatory cells were severely infiltrated,but pathology improved with time.In rats with sepsis and lung injury,HNL was positively cor-related with IL-6,IL-1β,TNF-α,lung wet/dry ratio,and lung injury scores(all P＜0.05),while negatively corre-lated with oxygenation index(P＜0.05).Conclusion In rats with sepsis lung injury,HNL increases significantly,with severe inflammation and aggravation in lung tissue wet/dry ratio and lung injury,while oxygenation index de-creases.HNL level is positively correlated with IL-6,IL-1β,TNF-α levels,lung tissue wet/dry ratio and lung inju-ry,but negatively correlates with oxygenation index.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment