Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Reach-to-grasp movements require integrating information on both object location and grip type, but how these elements are planned and to what extent they interact remains unclear. We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays, requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures. Neural activity in the dorsal premotor cortex (PMd) revealed that reach and grasp were similarly represented yet not independent. Upon receiving the second cue, the PMd continued encoding the first, but over half of the neurons displayed incongruent modulations: enhanced, attenuated, or even reversed. Population-level analysis showed significant changes in encoding structure, forming distinct neural patterns. Leveraging canonical correlation analysis, we identified a shared subspace preserving the initial cue's encoding, contributed by both congruent and incongruent neurons. Together, these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd, providing insights into potential applications for brain-machine interfaces.
Animals ; Motor Cortex/physiology* ; Hand Strength/physiology* ; Macaca mulatta ; Psychomotor Performance/physiology* ; Neurons/physiology* ; Male ; Cues ; Movement/physiology* ; Gestures

Objective To observe MRI features of H3K27M mutant type and wild type astrocyte differentiated diffuse midline glioma(DMG)in spinal cord.Methods Totally 91 patients with astrocyte differentiation diffuse midline glioma(DMG)in spinal cord confirmed by pathology were retrospectively enrolled and divided into mutant group(n=44)and wild group(n=47)according to H3K27M status.Clinical and MRI manifestations were compared between groups,and logistic regression analysis was used to screen the impact factors of H3K27M mutation.Results The incidence of peritumoral edema and spinal cord cavity in mutant group were lower than those in wild group(both P＜0.05),while no significant difference of other parameters was found between groups(all P＞0.05).All clinical and MRI parameters were included in logistic regression analysis,and the result showed that they were not influencing factors of H3K27M mutation(all P＞0.05).Conclusion The incidence of peritumoral edema and spinal cord cavity in spinal cord H3K27M mutant type astrocyte differentiated DMG were lower than those of wild type,yet not sufficient to be regarded as impact factors for predicting H3K27M mutation of DMG.

Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.
Brain ; Cerebral Cortex ; Computer Simulation ; Electricity ; Magnetic Fields

Transcranial electric stimulation (TES) is a non-invasive, economical, and well-tolerated neuromodulation technique. However, traditional TES is a whole-brain stimulation with a small current, which cannot satisfy the need for effectively focused stimulation of deep brain areas in clinical treatment. With the deepening of the clinical application of TES, researchers have constantly investigated new methods for deeper, more intense, and more focused stimulation, especially multi-electrode stimulation represented by high-precision TES and temporal interference stimulation. This paper reviews the stimulation optimization schemes of TES in recent years and further analyzes the characteristics and limitations of existing stimulation methods, aiming to provide a reference for related clinical applications and guide the following research on TES. In addition, this paper proposes the viewpoint of the development direction of TES, especially the direction of optimizing TES for deep brain stimulation, aiming to provide new ideas for subsequent research and application.
Transcranial Direct Current Stimulation/methods* ; Deep Brain Stimulation ; Brain/physiology* ; Head ; Electric Stimulation/methods*

A 53-year woman and her 18-year daughter presenting with bone pain, bone fractures, bone deformities and short stature were admitted to Gansu Provincial People′s Hospital in March 2021. Laboratory tests showed low blood phosphorus, low renal phosphorus threshold, normal or low blood calcium, and normal or increased PTH. The high-throughput sequencing indicated heterozygous mutations of the PHEX gene (Phosphate-regulating gene with Homology to Endopeptidases on the X chromosome) in two patients, which was not detected in other family members; finally the diagnosis of X-linked dominant hypophosphatemic rickets/osteomalacia(XLH)was confirmed for these two patients. Treated with neutral phosphorus solution and Rocaltrol, bone pain was relieved completely in the younger patient, but not for her mother due to long disease course and severe complications. Because of the large heterogeneity of the disease there are high missed diagnosis and misdiagnosis rates for XLH. In this paper a pedigree of XLH is reported with literature review.

In transcranial magnetic stimulation (TMS), the conductivity of brain tissue is obtained by using diffusion tensor imaging (DTI) data processing. However, the specific impact of different processing methods on the induced electric field in the tissue has not been thoroughly studied. In this paper, we first used magnetic resonance image (MRI) data to create a three-dimensional head model, and then estimated the conductivity of gray matter (GM) and white matter (WM) using four conductivity models, namely scalar (SC), direct mapping (DM), volume normalization (VN) and average conductivity (MC), respectively. Isotropic empirical conductivity values were used for the conductivity of other tissues such as the scalp, skull, and cerebrospinal fluid (CSF), and then the TMS simulations were performed when the coil was parallel and perpendicular to the gyrus of the target. When the coil was perpendicular to the gyrus where the target was located, it was easy to get the maximum electric field in the head model. The maximum electric field in the DM model was 45.66% higher than that in the SC model. The results showed that the conductivity component along the electric field direction of which conductivity model was smaller in TMS, the induced electric field in the corresponding domain corresponding to the conductivity model was larger. This study has guiding significance for TMS precise stimulation.
Transcranial Magnetic Stimulation ; Diffusion Tensor Imaging ; Electric Conductivity ; Electricity ; Scalp