Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.