Second People Hospital of Hunan

ObjectiveTo evaluate the safety and effectiveness of lurasidone in Chinese patients with schizophrenia in a 12-week post-marketing study.MethodsThis 12-week, multicenter, prospective, open-label, single-arm study included schizophrenia patients from 36 sites in Mainland China, who initiated lurasidone between September 2019 and December 2023. Adverse events (AEs) and adverse drug reactions (ADRs) were primary safety endpoints. Other safety assessments included extrapyramidal symptoms (EPS) and weight gain. Effectiveness was evaluated using the Brief Psychiatric Rating Scale (BPRS) at baseline and week 12. Patients were also stratified to assess differences across ages.ResultsA total of 3170 patients were included in the Full Analysis Set (FAS) and 3178 in the Safety Set (SS). The mean daily lurasidone dose was 59.9±20.93 mg. ADRs occurred in 7.9% of patients, with incidences of 8.1%, 8.9%, 5.9%, and 2.3% in the <18, 18–45, 45–65, and >65-year age groups, respectively. EPS was the most common ADR (3.2%), typically emerging in weeks 3–4. Metabolic-related AEs occurred in 4.3% and 2.2% of patients with and without metabolic affecting agents. BPRS scores significantly improved at weeks 2/4, 6/8, and 12 compared with baseline (all P < 0.05): total score (−8.9 ± 9.62, −14.0 ± 12.16, −17.5 ± 13.61), anxiety-depression (−1.5 ± 2.37, −2.5 ± 2.88, −3.3 ± 3.31), anergia (−1.5 ± 2.34, −2.4 ± 2.83, −3.1 ± 3.11), thought disturbance (−2.4 ± 2.98, −3.8 ± 3.72, −4.7 ± 4.07), activation (−1.2 ± 1.97, −1.7 ± 2.38, −2.1 ± 2.63), and hostility-suspiciousness (−2.4 ± 2.81, −3.6 ± 3.44, −4.3 ± 3.76). In <18 years group, BPRS total score also significantly decreased from 46.1±15.10 at baseline to 26.3±9.72 at week 12.ConclusionThis real-world study demonstrated a favorable safety profile and significant clinical effectiveness of lurasidone in both adult and adolescent population with schizophrenia in China in real-world clinical settings, supporting its use across diverse patient populations.Trial RegistrationShanghai Clinical Research Center for Mental Health (SCRC-MH) NCT04432688. URL: www.smhc.org.cn/.

The pharmaceutical crystal habit significantly influences downstream processing and product quality. However, traditional experimental screening methods rely heavily on empirical knowledge and trial-and-error experimentation, demanding substantial resources and time. Here we present an interpretable machine learning framework integrating molecular descriptors with quantum chemical (QC) or thermodynamic (HSP, PC-SAFT) parameters to predict crystal habits. Using a curated database of 418 entries covering 153 APIs and 41 solvents, the XGBoost model demonstrated superior performance among seven algorithms. Models augmented with QC or thermodynamic descriptors significantly improved prediction, achieving AUC > 0.88. SHAP analysis revealed dipole moments and solubility parameter differences as key determinants of crystal habit, enhancing interpretability. External validation on six compounds in seven solvents confirmed that models with additional mechanistic descriptors consistently outperformed the molecular-only baseline, with the Molecular+QC model showing the best overall performance. This proposal paves the way to the rational design of crystal engineering strategies for habit prediction and control, and offers a general framework that can readily be extended to other crystallographic applications, as well as broader domains, including drug discovery and materials science.

Retrospective studies suggest that early time-of-day (ToD) infusions of immunochemotherapy may improve efficacy. However, prospective randomized controlled trials are needed to validate it. In this randomized phase 3 LungTIME-C01 trial, 210 patients with treatment naive stage IIIC-IV non-small cell lung cancer (NSCLC) lacking driver mutations were randomly assigned in a 1:1 ratio to either an early or late ToD group, defined by the administration of the first four cycles of an anti-PD-1 agent before or after 15:00 h. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS) and objective response rate (ORR). After a median follow-up of 28.7 months, the median PFS was 11.3 months (95% confidence interval (CI) = 9.2-13.4) in the early ToD group and 5.7 months (95% CI = 5.2-6.2) in the late ToD group, corresponding to a hazard ratio (HR) for earlier disease progression of 0.40 (95% CI = 0.29-0.55; P < 0.001). The median OS was 28.0 months (95% CI = not estimable (NE)-NE) in the early ToD group and 16.8 months (95% CI = 13.7-19.9) in the late ToD group, corresponding to an HR of an earlier death of 0.42 (95% CI = 0.29-0.60; P < 0.001). Treatment-related adverse events were consistent with the established safety profile, with no new safety signals observed. No significant differences in immune-related adverse events were observed between the two groups. Over the first four cycles, morning circulating CD8+ T cells increased in the early ToD group, whereas they declined in the late ToD group (P < 0.001). Furthermore, the ratio of activated (CD38+ HLA-DR+) versus exhausted (TIM-3+PD-1+) CD8+ T cells was higher in the early ToD group (P < 0.001) compared with the late ToD group (P < 0.001). In summary, our study indicates that early ToD immunochemotherapy substantially improves PFS and OS and is associated with enhanced antitumor CD8+ T cell characteristics compared with late ToD treatment. ClinicalTrials.gov registration: NCT05549037 .

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, insulin resistance, and insufficient insulin secretion. Despite existing therapeutic strategies, challenges such as inadequate treatment adherence and psychological stress often result in suboptimal blood glucose control. This study investigates the effectiveness of a traditional Chinese medicine (TCM) syndrome differentiation-based nursing model in managing T2DM, aiming to improve blood glucose control, physical health, quality of life, and psychological state. This retrospective cohort study enrolled 125 T2DM patients from the endocrinology clinic between April 2023 and November 2024. Participants were divided into 2 groups: the observation group (TCM syndrome differentiation-based nursing model) and the control group (conventional nursing care). Various outcomes were assessed, including blood glucose management (fasting plasma glucose, 2-hour postprandial blood glucose, glycated hemoglobin), physical indicators (body mass index, waist circumference, waist-to-height ratio), food craving (Food Cravings Trait Questionnaire), quality of life (Diabetes Quality of Life Scale), and psychological state (Self-Rating Anxiety Scale and Self-Rating Depression Scale). The observation group showed significantly greater reductions in fasting plasma glucose, 2-hour postprandial blood glucose, and glycated hemoglobin (P < .001), compared to the control group (P < .05). Physical indicators (body mass index, waist circumference, and waist-to-height ratio) also improved significantly (P < .001), with greater improvements than the control group (P < .05). Additionally, the observation group had notably better scores for food craving (Food Cravings Trait Questionnaire) and quality of life (Diabetes Quality of Life Scale), and anxiety (Self-Rating Anxiety Scale) and depression (Self-Rating Depression Scale) scores decreased significantly (P < .05). The TCM syndrome differentiation-based nursing model significantly improves blood glucose control, physical health, dietary control, quality of life, and psychological well-being in T2DM patients, suggesting its important clinical application value.

BackgroundThe flipped classroom (FC) is increasingly used in medical education, but the impact of a continuous FC strategy on anesthesiology learning and career choice in eight-year medical program students remains unclear.MethodsIn a randomized trial, 200 students received either continuous FC (n=100) or traditional (n=100) anesthesiology instruction. Outcomes included final exam scores, survey-assessed satisfaction, active learning, critical thinking, and post-course specialty selection. Mediation analysis evaluated how a weighted composite of these scores influenced anesthesiology major selection.ResultsThe continuous FC group demonstrated significantly higher final exam scores, satisfaction, and active learning levels (all P < 0.05). Most importantly, students in the FC group were 21.77 times more likely to choose anesthesiology as their specialty than those in the control group (OR = 21.77, 95% CI: 1.79–264.83, P = 0.016). Mediation analysis indicated that 44.13% of the total effect of the FC intervention on specialty choice was mediated by improvements in the weighted composite score (indirect effect: β = 0.059, 95% CI: 0.024–0.102, P = 0.005).ConclusionThe continuous FC approach enhances learning outcomes, fosters essential skills, and significantly increases the selection of anesthesiology as a specialty. This demonstrates its substantial positive impact and potential value in addressing specialty shortages in medical education.

Lung cancer remains a significant medical problem in Asia, and improved treatments are needed for patients diagnosed with non-small cell lung cancer (NSCLC), who are frail with poor performance status or substantial comorbidities. This study aimed to investigate the efficacy and safety of first-line atezolizumab vs. single-agent chemotherapy in the Asian subpopulation in IPSOS trail. This exploratory analysis of the Asian subpopulation from the phase 3, global, open-label, randomized controlled IPSOS trial evaluated the efficacy and safety of atezolizumab (1200 mg intravenously every 3weeks) vs. single-agent chemotherapy (investigator's choice of vinorelbine or gemcitabine) as first-line treatment in patients with locally advanced or metastatic NSCLC, who were ineligible for platinum-based chemotherapy. The primary outcome was overall survival (OS); other outcomes were progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety. Seventy patients from China and Vietnam were included. Median OS was 15.8 months in the atezolizumab group vs. 12.5 months in the chemotherapy group; unstratified hazard ratio, 0.74 (95% confidence interval 0.41, 1.35). Median PFS was 8.1 months vs. 5.4 months, ORR was 27.9% vs. 7.4%, and median DOR was 18.7 months vs. 9.3 months, in the atezolizumab group vs. in the chemotherapy group, respectively. All-grade and grade 3-4 treatment-related adverse events (AEs) were less frequent with atezolizumab compared with chemotherapy. Two patients in the atezolizumab group had grade 5 AEs, namely pneumonia and acute left ventricular failure, with the latter considered treatment-related. Atezolizumab showed encouraging efficacy results and was well tolerated in an Asian subpopulation of patients with NSCLC who were deemed ineligible for standard platinum-based chemotherapy. The findings of this exploratory subpopulation analysis were consistent with those for the global IPSOS population. ClinicalTrials.gov, NCT03191786.

Hypertrophic scarring (HS) is a dermal fibroproliferative disorder accompanied by pain. Sildenafil (SIL) has been shown to have a protective effect against fibrosis. This study aimed to determine the effects and mechanisms of SIL on the proliferation, migration, and extracellular matrix (ECM) production of HS fibroblasts. The expression levels of Krüppel-like factor 15 (KLF15) and lysyl oxidase-like 1 (LOXL1) in human dermal fibroblasts (HDFbs) and HS-derived fibroblasts (HSFbs) were determined using reverse transcription-quantitative polymerase chain reaction and Western blotting. The effect of SIL on cell proliferation, migration, ECM production, and SMAD expression was assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, transwell, and Western blotting assays, respectively. The effect of KLF15 on LOXL1 transcriptional activity was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. Compared with HDFbs, HSFbs showed greater migration and ECM deposition. SIL inhibited cell proliferation, migration, ECM deposition, and SMAD activation in HSFbs, whereas these effects were inhibited by KLF15 knockdown. KLF15 inhibited LOXL1 transcription in HSFbs. LOXL1 silencing abrogated the effect of KLF15 knockdown on SIL-inhibited proliferation, migration, and ECM deposition. SIL inhibited the transcriptional activity of LOXL1 by upregulating KLF15, eventually inactivating SMAD signaling and suppressing the proliferation, migration, and ECM deposition of HSFbs.

ABSTRACTBackgroundMiller−Fisher syndrome (MFS) is a recognized clinical variant of Guillain−Barré syndrome (GBS), characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia. When accompanied by additional symptoms such as bulbar palsy, limb weakness, or lethargy, it is termed MFS overlap syndrome.Case PresentationThis report describes a male patient diagnosed with MFS overlap syndrome, presenting with ophthalmoplegia, ataxia, bulbar palsy, numbness in both arms, positive GM4 IgG antibodies, a persistent, intractable headache, and a delayed onset of left‐sided peripheral facial palsy. The patient had a preceding suspected case of chlamydial pneumonia before symptom onset, and his condition improved significantly following treatment with intravenous immunoglobulin.ConclusionThis case suggests that chlamydial pneumonia might predispose individuals to GBS. Patients with MFS/pharyngeal‐cervical‐brachial (PCB) overlap syndrome may exhibit atypical symptoms, including persistent, intractable headaches, and delayed peripheral facial paralysis. Atypical symptoms should not delay the diagnosis and treatment of GBS once other conditions have been adequately excluded. The presence of anti‐GM4 antibodies, often found alongside other anti‐ganglioside antibodies, may serve as a critical immunological factor in MFS/PCB overlap syndrome.