ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective To observe the effect of Renshen(ginseng)-Yuzhu(fragrant solomonseal rhizome)on inflammatory factors and inflammasomes in depression rats,and to explore the antidepressant mechanism of Renshen-Yuzhu.Methods Fifty male SD rats were divided into the blank group,model group,fluoxetine group(2.1 mg/kg),Renshen-Yuzhu low-dose group(1.89 g/kg),and Renshen-Yuzhu high-dose group(5.67 g/kg),with ten rats in each group.Except for the blank group,the rats in the other groups were treated with chronic unpredictable mild stress to establish a depression rat model.On the second day after the end of modeling,the rats in each group were given the corresponding drugs once daily for 14 days.After modeling and dosing,body weight,forced swimming immobility time,and sucrose preference rate were measured.After dosing,hematoxylin-eosin staining was used to detect neuronal damage in the cerebral cortex,enzyme-linked immunosorbent assay was used to detect the contents of interleukin-4(IL-4),interleukin-23(IL-23),and interleukin-27(IL-27)in cortex,real-time PCR was used to detect the mRNA expression of interleukin-24(IL-24)in cortex,and the protein expressions of nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1),absent in melanoma 2(AIM2),and nucleotide-binding oligomerization domain-like receptor protein 4(NLRC4)were detected by Western blotting.Results After dosing,compared with the blank group,the body weight of the model group decreased,the sucrose preference rate decreased,the swimming immobility time was prolonged,the neuronal tissue in cortex was destroyed,the content of IL-4 in cortex decreased,the contents of IL-23 and IL-27 in cortex increased,and the protein expressions of NLRP1,AIM2 and NLRC4 in cortex increased(P＜0.01).Compared with the model group,the body weight of rats in each administration group increased,the sucrose preference rate increased,the swimming immobility time was shortened,the damage of neuronal tissues in cortex improved,the content of IL-4 in cortex increased,the contents of IL-23 and IL-27 in cortex decreased,and the protein expressions of NLRP 1,AIM2 and NLRC4 in cortex decreased(P＜0.05).Conclusion Renshen-Yuzhu couplet medicines can improve the depressive-like behavior and exert antidepressant effect in chronic stress rats,and its mechanism may be related to the inhibition of NLRP 1,NLRC4,AIM2 inflammasome activation and its mediated inflammatory response in cortex,reducing pro-inflammatory cytokines,and increasing the level of antiinflammatory cytokines.

Robotic surgery is known as the"third technological revolution"in the field of surgery,and is an important milestone in the development of modern surgery.However,our country's innovative surgical robot industry is still in its early stages,and it is only being utilized in certain surgical fields.To explore the effectiveness of the application of do-mestic surgical robot in oral and maxillofacial surgery,the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot.The operation was successful,facial nerve function was preserved,and postoperative wound healing was good.

Traditional open head and neck surgery often leaves permanent scars,significantly affecting appearance.The emergence of surgical robots has introduced a new era for minimally invasive surgery.However,the complex anatomy of the head and neck region,particularly the oral and maxillofacial areas,combined with the high costs associated with established systems such as the da Vinci,has limited the widespread adoption of surgical robots in this field.Recently,surgical robotic platform in China has developed rapidly,exemplified by the promise shown by the KangDuo Surgical Robot(KD-SR).Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery,its performance in complex head and neck regions remains untested.This study evaluated the feasibility,effectiveness,and safety of the newly developed KD-SR-01,comparing it with standard endoscopic systems in head and neck procedures on porcine models.We performed parotidectomy,submandibular gland resection,and neck dissection,collected baseline characteristics,perioperative data,and specifically assessed cognitive workload using the NASA-TLX.None of the robotic procedures were converted to endoscopic or open surgery.The results showed no significant difference in operation time between the two groups(P=0.126),better intraoperative bleeding control(P=0.001),and a significant reduction in cognitive workload(P<0.001)in the robotic group.In conclusion,the KD-SR-01 is feasible,effective,and safe for head and neck surgery.Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.

Traditional open head and neck surgery often leaves permanent scars,significantly affecting appearance.The emergence of surgical robots has introduced a new era for minimally invasive surgery.However,the complex anatomy of the head and neck region,particularly the oral and maxillofacial areas,combined with the high costs associated with established systems such as the da Vinci,has limited the widespread adoption of surgical robots in this field.Recently,surgical robotic platform in China has developed rapidly,exemplified by the promise shown by the KangDuo Surgical Robot(KD-SR).Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery,its performance in complex head and neck regions remains untested.This study evaluated the feasibility,effectiveness,and safety of the newly developed KD-SR-01,comparing it with standard endoscopic systems in head and neck procedures on porcine models.We performed parotidectomy,submandibular gland resection,and neck dissection,collected baseline characteristics,perioperative data,and specifically assessed cognitive workload using the NASA-TLX.None of the robotic procedures were converted to endoscopic or open surgery.The results showed no significant difference in operation time between the two groups(P=0.126),better intraoperative bleeding control(P=0.001),and a significant reduction in cognitive workload(P<0.001)in the robotic group.In conclusion,the KD-SR-01 is feasible,effective,and safe for head and neck surgery.Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.

Acid-base dissociation constant (pK_a) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pK_a prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pK_a (multi-fidelity modeling with subgraph pooling for pK_a prediction), a novel pK_a prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledge-aware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pK_a prediction. To overcome the scarcity of accurate pK_a data, low-fidelity data (computational pK_a) was used to fit the high-fidelity data (experimental pK_a) through transfer learning. The final MF-SuP-pK_a model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pK_a achieves superior performances to the state-of-the-art pK_a prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pK_a achieves 23.83% and 20.12% improvement in terms of mean absolute error (MAE) on the acidic and basic sets, respectively.