Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

Objective: To explore whether the long-term and frequent use of citrate anticoagulants negatively affects the bone metabolism balance of female frequent plateletpheresis donors, so as to better protect their health. Methods: A total of 65 female plateletpheresis donors and 55 female whole-blood donors from Guangzhou Blood Center (May to December 2024) were enrolled as experimental and control groups respectively, stratified into age subgroups (18-39 years and 40-60 years). Serum levels of 25-hydroxyvitamin D [25(OH)D], procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and type I collagen carboxy-terminal telopeptide (CTX) were measured. Differences in bone metabolism markers between experimental and control groups across age subgroups were compared. ANOVA was used to analyze dose-response relationships between donation age, annual apheresis donation frequency, and biochemical indicators. Results: In the 40-60 age subgroup, 25(OH)D levels were significantly lower in the experimental group (P<0.05), exhibiting a linear increase with age and a linear decrease with annual donation frequency. No significant differences in CTX or PINP levels were observed between experimental and control groups in either age subgroup. Conclusion: High-frequency plateletpheresis donation does not disrupt bone metabolic balance in female donors. However, it is associated with reduced vitamin D levels in female donors aged >40 years, potentially increasing the risk of osteoporosis. Vitamin D supplementation is recommended for high-frequency female plateletpheresis donors in this age group.

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:Deep muscle stimulation has the effects of releasing muscle adhesion,relieving muscle spasm,improving and restoring muscle compliance and elasticity.Electromyographic biofeedback therapy can promote nerve recovery and improve lower limb motor function and gait. OBJECTIVE:To observe the effect of the effect of deep muscle stimulation combined with electromyographic biofeedback therapy on the spasm of the triceps surae and gait changes after stroke by using a digital muscle detector and three-dimensional gait analysis system. METHODS:A total of 72 patients who met the inclusion criteria were selected from the Rehabilitation Department of the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2020 to October 2023.And they were enrolled and randomly divided into two groups(n=36 per group):a control group and a combined group.The control group received routine rehabilitation therapies,electromyographic biofeedback and pseudo deep muscle stimulation,while the combined group received true deep muscle stimulation treatment on the basis of the control group,five times per week,for 4 consecutive weeks.The oscillation frequency and dynamic stiffness of the affected gastrocnemius muscle,active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,Fugl-Meyer assessment of the lower limbs,and three-dimensional gait analysis parameters were statistically analyzed before and after treatment in two groups. RESULTS AND CONCLUSION:After treatment,oscillation frequency and dynamic stiffness values of the inner and outer sides of the affected gastrocnemius muscle in both groups of patients were significantly reduced compared with before treatment(P<0.05),and the combined group showed a more significant decrease compared with the control group(P<0.05).The active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,and Fugl-Meyer scores after treatment were significantly increased or improved compared with before treatment(P<0.05),while the combined group showed a more significant increase or improvement compared with the control group(P<0.05).In terms of gait parameters,the walking speed,frequency,and stride in both groups of patients were significantly increased compared with before treatment(P<0.05),while the combined group showed a more significant increase compared with the control group(P<0.05).The percentage time of support phase on the healthy side was shortened compared with before treatment(P<0.05),while the combined group showed a more significant decrease compared with the control group(P<0.05).In addition,there was no significant difference between the two groups except for the percentage of healthy side support(P>0.05).To conclude,the combination of deep muscle stimulation and electromyographic biofeedback can effectively alleviate triceps spasm in the short term after stroke,improve ankle dorsiflexion function,enhance lower limb motor function,and improve gait.The treatment effect is significant and worthy of clinical promotion and application.

BACKGROUND:Osteoporotic vertebral fractures are the most common complication in patients with osteoporosis.As a new imaging technique,spine magnetic resonance imaging(MRI)is much more sensitive than X-ray film in the diagnosis of osteoporotic vertebral fractures.However,total spine MRI is costly and takes a long time to scan.Therefore,there is no consensus on whether all patients with osteoporotic vertebral fractures need to undergo total spine MRI scan and which patients need to undergo total spine MRI. OBJECTIVE:To analyze the distribution characteristics of vertebral fractures and explore their clinical significance by observing the whole spine MRI data of osteoporotic vertebral fractures patients. METHODS:Data of cases and MRI images of all patients diagnosed with fresh osteoporotic vertebral fractures who visited the Department of Orthopedics,Affiliated Hospital of Southwest Medical University from August 2018 to September 2022 were retrospectively analyzed.903 patients were included in the study based on inclusion and exclusion criteria.General information(age,gender,and body mass index),medical history characteristics(duration of illness,history of trauma surgery,percussion pain area,and pain score)were collected.The characteristics of vertebral fractures were analyzed through whole spine magnetic resonance imaging.Firstly,based on the number of vertebral fractures in patients,they were divided into the single vertebral fracture group(484 cases)and the multi-vertebral fracture group(419 cases),and the differences were analyzed between the two groups.Then,based on whether the farthest interval between the fractured vertebrae was greater than or equal to 5,the multi vertebral fracture group was further divided into two subgroups.Among them,Group A(the farthest interval between the fractured vertebrae was less than 5)contained 306 cases;Group B(with the farthest interval between fractured vertebral bodies greater than 5)included 113 cases.The differences were analyzed between two subgroups. RESULTS AND CONCLUSION:(1)Among 903 patients,419 patients(46.4%)had more than two fractured vertebrae.There were 654 patients(72.4%)with thoracolumbar fractures,and 54 patients(6%)with fractures in the thoracic plus lumbar region and the entire thoracic to lumbar region.In group B,96.5%of patients had multiregional percussion pain.(2)Compared with the patients in the single vertebral fracture group and the multi-vertebral fracture group,there were significant differences in bone mineral density,whether the medical history was greater than or equal to 1 month,the history of low energy injury,and the distribution and number of axial percussion pain areas in the spine during physical examination between the two groups(P<0.05).Age,gender,body mass index,whether there was underlying disease,pain visual analog scale score,whether there was a history of elderly thoracolumbar fracture,and whether there was a history of thoracolumbar surgery,and the number of fractured vertebrae had no statistical significance(P>0.05).(3)There were statistically significant differences between the Groups A and B in bone mineral density,the distribution and quantity of percussion pain area,and the history of low energy injury(P<0.05).There were no significant differences in age,gender,history of old fractures,visual analog scale score,body mass index,whether the medical history was longer than or equal to 1 month,history of underlying diseases,and history of thoracolumbar surgery between the two groups(P>0.05).(4)Patients with multiple low-energy trauma history,history of more than 1 month,multiple percussion pain,and the lower bone mineral density should be alert to the occurrence of multiple vertebral fracture and jump fracture.We recommend the whole spinal MRI for these patients.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To investigate the efficacy of phloroglucinol combined with ballon dilation in promoting cervical ripening and shortening labor duration in full-term primiparas and its effects on maternal and neonatal outcomes.Methods:A randomized controlled study was conducted on 60 full-term primiparas who delivered at the First People's Hospital of Longnan from January 2022 to December 2023. The subjects were randomly divided into a control group and an observation group ( n = 30/group) using the random number table method. The control group underwent ballon dilation for cervical ripening, while the observation group received intravenous injection of 80 mg phloroglucinol in addition to ballon dilation. Cervical ripening effect, labor duration, delivery mode, and the incidence of adverse pregnancy outcomes were observed in both groups. Results:The score of cervical ripening in the observation group was significantly higher than that in the control group [(8.31 ± 0.93) vs. (7.83 ± 0.85), t = 2.09, P = 0.041]. The duration of the first stage of labor, the duration of the second stage of labor, and the total duration of labor were (482.7 ± 18.2) minutes, (38.3 ± 10.7) minutes, and (526.6 ± 21.2) minutes, respectively. All these durations were significantly shorter than those in the control group [(521.3 ± 16.4) minutes, (45.7 ± 8.3) minutes, (573.4 ± 18.5) minutes, t = 2.62, 4.32, 12.80, all P<0.05]. The amount of postpartum bleeding in the observation group was significantly lower than that in the control group [(322.5 ± 21.2) mL vs. (341.9 ± 32.5) mL, t = -3.87, P<0.001]. There were no statistically significant differences in the Apgar scores and neonatal behavioral neurological assessment scores between the two groups (both P>0.05). Conclusions:The use of phloroglucinol combined with ballon dilation can effectively promote cervical ripening in full-term primiparas, shorten labor duration, improve induction success rates, and reduce postpartum hemorrhage. Therefore, this combined treatment significantly enhances maternal and neonatal outcomes while demonstrating high safety.

Objective:To study the relationship between serum levels of angiopoietin-2 (Ang-2), insulin-like growth factor 1 (IGF-1), immune factors, and prognosis in patients with uterine fibroids.Methods:A case-control study was conducted involving 93 patients with uterine fibroids who underwent laparoscopic myomectomy at The First People's Hospital of Longnan City between June 2021 and June 2023. These patients constituted the study group. Additionally, 104 healthy women undergoing routine health check-ups during the same period were selected as the control group. Based on the prognosis of the patients in the study group, they were further divided into two subgroups: a good prognosis group ( n = 42) and a poor prognosis group ( n = 46). The correlations among serum levels of Ang-2, IGF-1, immune factors, and prognosis were analyzed in the study group compared to the control group, as well as between the good prognosis and poor prognosis groups. Results:Four cases from the control group and five cases from the study group were excluded from the analysis. In the study group, serum levels of Ang-2 and IGF-1 were found to be (303.18 ± 42.39) mg/L and (1377.11 ± 84.78) mg/L, respectively. Both levels were significantly higher than those in the control group [(231.25 ± 34.18) mg/L, (438.09 ± 52.15) mg/L, t = 12.87, 19.63, both P < 0.001]. Additionally, CD 8+ levels in the study group were higher than those in the control group ( t = -15.79, P < 0.001). Conversely, CD 3+, CD 4+, and CD 4+/CD 8+ levels were lower in the study group compared to the control group ( t = 7.92, 8.41, 5.21, all P < 0.001). In the poor prognosis group, the levels of Ang-2 and IGF-1 were (335.16 ± 42.67) mg/L and (1406.18 ± 83.77) mg/L, respectively, both of which were significantly higher than those in the good prognosis group [(284.63 ± 36.19) mg/L, (434.91 ± 53.28) mg/L, t = 5.96, 64.1, both P < 0.001]. The CD 8+ levels in the poor prognosis group were also higher than those in the good prognosis group ( t = -10.27, P < 0.001), while CD 3+, CD 4+, and CD 4+/CD 8+ levels were lower in the poor prognosis group ( t = 5.31, 7.03, 3.15, all P < 0.001). Correlation analysis revealed that Ang-2 was negatively correlated with CD 3+, CD 4+, and CD 4+/CD 8+ levels ( r = -0.623, -0.578, -0.662). In contrast, Ang-2 was positively correlated with CD 8+ levels, a history of uterine fibroids, the number of fibroids, a history of miscarriage, and the duration of breastfeeding ( r = 0.593, 0.452, 0.446, 0.419, 0.422). IGF-1 levels were also negatively correlated with CD 3+, CD 4+, and CD 4+/CD 8+ levels ( r = -0.720, -0.751, -0.712), while positively correlated with CD 8+, a history of uterine fibroids, the number of fibroids, a history of miscarriage, and the duration of breastfeeding ( r = 0.631, 0.503, 0.444, 0.501, 0.451). Furthermore, multivariate logistic regression analysis indicated that a family history of uterine fibroids, the number of fibroids, a history of miscarriage, and the duration of breastfeeding were all significant risk factors affecting the prognosis of patients with uterine fibroids (all P < 0.05). Conclusions:Patients with uterine fibroids have higher levels of Ang-2, IGF-1 and CD 8+, while the levels of CD 3+, CD 4+, and CD 4+/CD 8+ are lower. Additionally, the expression levels of Ang-2 and IGF-1 are associated with the patients' immune factors and prognosis.

Objective To analyze the effects of national centralized volume-based procurement(CVBP)on hospitaliza-tion expenses of patients undergoing artificial joint replacement under the Diagnosis-Related Group(DRG)payment model in a public hospital,and to provide evidence for advancing reforms in high-value medical consumables and healthcare payment sys-tems.Methods Data from patients undergoing artificial joint replacement in a tertiary public hospital in 2022 were collected.Statistical analysis was used to assess the surplus and deficit of DRG year-end settlements for these cases.By comparing cost com-positions across different medical insurance types,differences in total inpatient medical expenses,out-of-pocket payments,per-sonal medical insurance account expenditures,and pooled fund reimbursements were evaluated before and after CVBP implemen-tation.Results Following CVBP implementation,the sample hospital demonstrated significant improvements in reducing medical costs,alleviating patient financial burdens,and optimizing medical insurance fund utilization.Under the DRG payment model,operational performance remained stable.Post-CVBP,total hospitalization expenses,patient out-of-pocket payments,and pooled fund reimbursements all decreased significantly(P＜0.001).Conclusion The practice of centralized procurement of artificial joints can be extended to other high-value medical consumables,continuously promoting the reform of the medical and health sys-tem,and ultimately achieving mutually beneficial and sustainable development among healthcare providers,insurers,and patients.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.