ObjectiveTo explore the effect of elbow-wrist functional orthosis on plantar pressure distribution and balance function in stroke patients with hemiplegia. MethodsFrom June, 2024 to April, 2025, 60 patients with post-stroke hemiplegia were recruited from Huashan Hospital, Fudan University, and Shanghai Hebin Rehabilitation Hospital. They were randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine neurological rehabilitation, while the intervention group received additional training with an elbow-wrist functional orthosis on the affected side, for eight weeks. Before and after intervention, the Modified Ashworth Scale (MAS) of the elbow joint, plantar pressure symmetry index (SI), plantar contact area and mean plantar pressure were recorded, and balance and mobility were assessed using the Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-Meter Walk Test (10MWT). ResultsTwo cases dropped out in the control group. After treatment, MAS grades of the elbow joint, forefoot SI, affected side plantar pressure area, BBS scores, TUGT and 10MWT of both groups improved (|Z| > 3.969, |t| > 3.528, P < 0.01), while the hindfoot SI and average pressure of the affected foot improved in the intervention group (∣t∣ > 4.264, P < 0.001). Except for TUGT and 10MWT, the intervention group was superior to the control group (∣Z∣ > 2.030, ∣t∣ > 2.096, P < 0.05). ConclusionThe elbow-wrist functional orthosis can enhance balance function in stroke patients with hemiplegia by reducing upper-limb spasticity, optimizing center-of-gravity distribution, and improving postural control.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Objective To determine the related substances in esmolol hydrochloride injection by HPLC method. Methods A Waters XBridge TM C₁₈ （4.6 mm×150 mm,5 µm） column packed with octadecylsilane-bonded silica gel was used, with phosphate buffer （3.0 g of potassium dihydrogen phosphate was taken, dissolved in water and diluted to 650 ml）-acetonitrile-methanol （65∶15∶20） as the mobile phase A, and mobile phase A mixed with methanol （65∶35） as the mobile phase B. The related substances in the test sample and those generated after forced degradation were qualitatively and quantitatively analyzed by the impurity reference standard method, with an injection volume of 20 μl, a column temperature of 30℃, a flow rate of 1.0 ml/min and a detection wavelength of 222 nm. Results The separation between esmolol hydrochloride and neighboring impurities as well as between each impurity was greater than 1.5; the impurities showed good linearity in their respective linear ranges （r>0.999）. The average recovery of impurity a （Imp-a） was 99.1% with an RSD of 0.56%; the average recovery of impurity b（Imp-b）was 96.0% with an RSD of 0.98%; the average recovery of impurity c （Imp-c） was 100.7% with an RSD of 1.24%; the average recovery of impurity d （Imp-d） was 99.0% with an RSD of 0.12%; the average recovery of impurity e （Imp-e） was 100.7% with an RSD of 0.64%; and the impurity f （Imp-f） average recovery was 101.7% with an RSD of 3.26%; impurity g （Imp-g） average recovery was 99.1% with an RSD of 1.45%. Conclusion This method could evaluate the quality of esmolol hydrochloride injection more accurately than the current standard and could provide data reference for the quality evaluation system.

Objective: To investigate the predictive value of preoperative Neutrophil-to-Lymphocyte Ratio (NLR), serum albumin (ALB), and their combination for perioperative RBC transfusion in patients with hepatocellular carcinoma. Methods: A total of 1 027 patients clinically diagnosed with hepatocellular carcinoma who underwent radical surgery were retrospectively analyzed. The patients were divided into transfusion group and non-transfusion group according to whether they received red blood cell suspension transfusion. The perioperative clinical data of patients were compared between the groups. The predictive value of NLR combined with ALB for perioperative blood transfusion was analyzed by receiver operating characteristic (ROC) curve, and the optimal cutoff value was determined. Results: A total of 207 patients (20.16%, 207/1 027) received RBC transfusion. NLR combined with serum ALB concentration (ROC=0.712; P<0.001) was more accurate in predicting transfusion demand than NLR or ALB alone. The transfusion rate in the group with NLR>2.12 and ALB≤40.5 (45.32%, 92/203) was significantly higher than that in the group with NLR≤2.12 and ALB>40.5 (13.01%, 51/392) and the remaining combination group (14.81%, 64/432). Correlation analysis showed that NLR was statistically significantly correlated with ASA score, vascular invasion, satellite data, and the extent of liver resection. ALB was significantly correlated with ASA score, TNM stage, vascular invasion, satellite, and extent of hepatectomy. Conclusion: This study demonstrates that the combination of preoperative inflammatory factor NLR and serum ALB can effectively predict the perioperative blood transfusion needs of patients with hepatocellular carcinoma.

Objective To explore the correlation and dose-response relationship between blood lipid parameters and the risk of thyroid nodules (TNs) in euthyroid women, providing references for disease prevention. Methods A case-control study was conducted, including 1 412 euthyroid women (701 in the case group and 711 in the control group). Crude and multivariable logistic regression models were used to assess the association between blood lipid parameters and the risk of TNs, and restricted cubic spline regression was applied to explore the dose-response relationship. Results Compared with women in the lowest quartile of serum triglyceride (TG; Q1, TG≤0.92 mmol/L), the risk of TNs was 45% (OR＝1.45, 95%CI 1.06-1.98) higher for those in Q2 (TG 0.93-1.24 mmol/L), 101% (OR＝2.01, 95%CI 1.47-2.77) higher for those in Q3 (TG 1.25-1.81 mmol/L), and 67% (OR＝1.67, 95%CI 1.19-2.33) higher for those in Q4 (TG>1.81 mmol/L) after adjusting for age, body mass index (BMI) and education. For each unit increase in log₁₀TG, the risk increased by 98% (OR＝1.98, 95%CI 1.14-3.45). Moreover, the correlation remained statistically significant even after further adjustment for thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) and urinary iodine (OR＝1.75, 95%CI 1.00-3.06, P＜0.05). However, correlations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with the risk of TNs were not statistically significant. Restricted cubic spline regression analysis further demonstrated the non-linear dose-response relationship of TG levels with the risk of TNs. Specifically, the risk of TNs increased in a monotonic manner at lower TG concentrations (＜1.23 mmol/L), but appeared to plateau or even slightly decrease at higher levels of TG (≥1.23 mmol/L). Conclusions Among euthyroid women, higher serum TG level is associated with risk of TNs, and this correlation is non-linear.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*