This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

OBJECTIVE: To explore the effect of nano-hydroxyapatite/collagen composite (nHAC) on bone graft fusion after anterior cervical discectomy and fusion (ACDF) in patients with cervical spondylosis and low bone mass. METHODS: A retrospective analysis was conducted on 47 patients with low bone mass who underwent ACDF from 2017 to 2021. They were divided into the nHAC group and the allogeneic bone group according to different bone graft materials. The nHAC group included 26 cases, with 8 males and 18 females;aged 50 to 78 years old with an average of (62.81±7.79) years old;the CT value of C₂-C₇ vertebrae was (264.16±36.33) HU. The allogeneic bone group included 21 cases, with 9 males and 12 females;aged 54 to 75 years old with an average of (65.95±6.58) years old;the CT value of C₂-C₇ vertebrae was (272.39±40.44) HU. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) spinal cord function score were compared before surgery, 1 week after surgery, and at the last follow-up to evaluate the clinical efficacy. Imaging assessment included C₂-C₇ Cobb angle, surgical segment height, intervertebral fusion, and whether the cage subsidence occurred at 1 week after surgery and the last follow-up. RESULTS: The follow-up duration ranged from 26 to 39 months with an average of (33.27±3.34) months in the nHAC group and 26 to 41 months with an average of (31.86±3.57) months in the allogeneic bone group. At 1 week after surgery and the last follow-up, the VAS, NDI scores, and JOA scores in both groups were significantly improved compared with those before surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the C₂-C₇ Cobb angles in the nHAC group and the allogeneic bone group were (14.26±10.32)° and (14.28±8.20)° respectively, which were significantly different from those before surgery (P<0.05). At the last follow-up, the C₂-C₇ Cobb angles in both groups were smaller than those at 1 week after surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the height of the surgical segment in the nHAC group was (31.65±2.55) mm, and that in the allogeneic bone group was (33.63±3.26) mm, which were significantly different from those before surgery (P<0.05). At the last follow-up, the height of the surgical segment in both groups decreased compared with that at 1 week after surgery, with statistically significant differences (P<0.05). At the last follow-up, 39 surgical segments were fused and 6 cages subsided in the nHAC group;40 surgical segments were fused and 7 cages subsided in the allogeneic bone group;there was no statistically significant difference between the two groups (P>0.05). Compared with the CT value of vertebrae without cage subsidence, the CT value of vertebrae with cage subsidence in both groups was significantly lower, with a statistically significant difference (P<0.05). CONCLUSION The application of nHAC in ACDF for patients with low bone mass can achieve effective fusion of the surgical segment. There is no significant difference in improving clinical efficacy, intervertebral fusion, and cage subsidence compared with the allogeneic bone group. With the extension of follow-up time, the C₂-C₇ Cobb angle decreases, the height of the surgical segment is lost, and the cage subsides in both the nHAC group and the allogeneic bone group, which may be related to low bone mass. Low bone mass may be one of the risk factors for cervical spine sequence changes, surgical segment height loss, and cage subsidence after ACDF.
Humans ; Male ; Female ; Middle Aged ; Spondylosis/physiopathology* ; Spinal Fusion/methods* ; Cervical Vertebrae/surgery* ; Aged ; Diskectomy ; Durapatite ; Retrospective Studies ; Collagen/chemistry*

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

Obesity and overweight remain major global public health challenges.In this paper,we examine current applications of digital nutrition technologies in weight management using the scoping review framework of Arksey and O'Malley.Visual recognition technologies have evolved from early-stage food image recognition into more advanced systems,although the vast diversity of food types continues to pose challenges for accuracy and generalizability.The combination of wearable devices and non-wearable sensors has increased the diversity of collected data and improved user comfort.Data integration and analysis tools,such as digital virtual twins,support personalized interventions by integrating multidimensional data.In addition,emerging applications have demonstrated encouraging clinical outcomes.However,existing studies have limitations,such as small sample sizes,high levels of information bias,and low evidence quality.Barriers,such as limited accessibility and high initial costs,further constrain the scalability of digital nutrition tools.Future studies should focus on expanding sample sizes,improving population diversity,and developing effective assessment methods and adjustments for specific target populations.Privacy and data security concerns must also be addressed to ensure safe implementation.Overall,digital nutrition technologies offer a promising approach to weight management,but continuous efforts in research and cost reduction are needed to fully realize their potential in weight management and to promote health for all.

Objective To investigate the association between healthy lifestyle factors and cardiovascular biological aging,as well as the relative contributions of different lifestyle factors.Methods Based on the clinical biochemical data and anthropometric data from the baseline survey of the UK Biobank(UKB),the Klemera-Doubal method(KDM)was used to establish cardiovascular biological age(CBA),and CBA acceleration was calculated accordingly.Multiple linear regression models were used to estimate the associations between healthy lifestyle factors and CBA acceleration.Then,the Quantile g-computation(QGC)was applied to evaluate the relative contributions of different lifestyle factors to CBA acceleration,with further analyses conducted separately for male and female populations.Additionally,stratified analyses were performed based on age,sex,body mass index(BMI),racial background,and family history of cardiovascular diseases to examine population heterogeneity.Results A total of 251 478 participants were included in the study.Both the overall healthy lifestyle score and each of the 7 lifestyle factors were negatively associated with CBA acceleration(overall lifestyle score:β=-0.75,95%CI:-0.77 to-0.73).Regarding the relative contributions of different lifestyle factors,alcohol consumption and diet accounted for the highest proportions(25.8%and 25.7%,respectively).However,there were differences by sex—alcohol consumption contributed the most in men(29.5%),followed by diet(23.0%),while in women,diet contributed the most(34.5%)and alcohol consumption accounted for a relatively low proportion(5.5%).Stratified analyses suggested that sex,BMI,and race might be potential effect modifiers.Conclusion Lifestyle factors,as modifiable behaviors,can slow the rate of cardiovascular biological aging.Among these factors,alcohol consumption and diet may represent effective targets for intervention.

BACKGROUND:Currently,there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis.Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage,but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking. OBJECTIVE:To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS:The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb.According to the random number table method,they were divided into four groups.lncRNA group,miRNA group,ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1,lentivirus vector overexpressing miR-146a-5p,lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint,respectively.At 4,8 and 12 weeks of modeling,cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups.At 4 weeks,the cartilage tissue of the lncRNA group showed swelling of chondrocytes,loss of cell polarity,destruction of extracellular matrix,surface erosion,fracture formation and partial or full layer loss of cartilage tissue.The degree of cartilage injury was gradually aggravated with time.The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups.qRT-PCR showed that at the same time point,mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups(P＜0.05).The mRNA expression levels of miR-146a-5p,aggrecan and type Ⅱ collagen were lower than those of the other three groups(P＜0.05).The mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction(P＜0.05).The mRNA expressions of miR-146a-5p,aggrecan and type Ⅱ collagen were higher than those of the ceRNA group and control group(P＜0.05).Western blot assay showed that at the same time point,the expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups(P＜0.05).The expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group(P＜0.05).The results showed that miR-146a-5p,as the target of NONHSAT248596.1,could be inhibited by the effect of its ceRNA.After acting on miR-146a-5p,NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein,type Ⅱ collagen,and aggrecan in osteoarthritis chondrocytes,resulting in the degradation of extracellular matrix and the loss of proteoglycan.

Objective:To explore the effects of melatonin on streptozotocin(STZ)-induced diabetic pulmonary fibrosis and regulatory mechanisms.Methods:C57BL/6 mice were randomly divided into the control group, STZ group, STZ+ low-dose melatonin(5 mg/kg) group, STZ+ high-dose melatonin(30 mg/kg) group using random number table, and a single intraperitoneal injection of STZ(150 mg/kg) was administered to establish a diabetic pulmonary fibrosis mouse model. Two weeks later, blood glucose levels ≥16.7 mmol/L confirmed successful modeling. Subsequently, melatonin was administered orally for 4 weeks, and the mice were sacrificed at 16 weeks for tissue sampling. Human umbilical vein endothelial cells were divided into the control group(glucose concentration is 5.5 mmol/L), high glucose group(glucose concentration is 33.3 mmol/L), high glucose+ low-dose melatonin(5 μmol/L) group, high glucose+ high-dose melatonin(20 μmol/L) group, and cells in each group were collected for subsequent detection after drug stimulation. Masson staining and immunofluorescence staining were used to observe fibrotic lesions, Western blotting was used to detect the expression related proteins, and sirtuin 3(Sirt3) siRNA was transfected to knock down Sirt3.Results:Significant fibrotic lesions were observed in the lung tissue of the STZ group compared to the control group, however, the STZ+ low-dose melatonin group and STZ+ high-dose melatonin group showed reduced fibrosis compared to the STZ group. In addition, compared to the control group, the endothelial cell marker platelet endothelial cell adhesion molecule-1(CD31) was significantly decreased in the STZ/high glucose group( P<0.001; P<0.001), and the interstitial fibrosis markers collagen 3, Vimentin, and α-smooth muscle actin(α-SMA) were significantly increased( P<0.001, P=0.035, P<0.001; P<0.001, P<0.001, P<0.001), but these trends were partially reversed after melatonin treatment in the STZ/high glucose+ low-dose melatonin group and the STZ/high glucose+ high-dose melatonin group. Moreover, the protein expression of Sirt3 was significantly reduced in the STZ/high glucose group compared to the control group( P<0.001; P<0.001), while it was increased in the STZ/high glucose+ low-dose melatonin and STZ/high glucose+ high-dose melatonin groups compared to the STZ/high glucose group( P=0.047, P<0.001; P=0.048, P<0.001). After transfecting Sirt3 siRNA to knock down the expression of Sirt3, the endothelial cell marker CD31 was significantly reduced( P=0.026), and interstitial fibrosis markers collagen 3, Vimentin, and α-SMA were significantly increased in the high glucose+ high-dose melatonin+ Sirt3 siRNA group compared to the high glucose+ high-dose melatonin group( P<0.001, P<0.001, P<0.001). Conclusion:Melatonin inhibits endothelial-mesenchymal transition by activating Sirt3 expression, thereby alleviating pulmonary fibrosis in STZ-induced diabetic mice.

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

Objective To investigate the difference between structured triglyceride(STG)and Non-structured triglyceride(NSTG)in nutritional support for perioperative patients.Methods A nationwide survey was conducted through online questionnaire.The questionnaire consisted of four modules:questionnaire information,patient information,prescription investigation and postoperative observation.SPSS 24.0 software was used for statistical analysis.Results Before and after parenteral nutrition(PN),the average levels of albumin(ALB)increased in both groups(P＜0.01),while the levels of C-reactive protein(CRP)and alanine aminotransferase(ALT)decreased(P＜0.01).The difference in serum triglyceride(TG)levels in the STG group was not statistically significant,while there was a decrease in the NSTG group(P＜0.05).Generalized linear equation analysis of repeated measurements showed that compared to the NSTG group,the increase in ALB levels in the STG group patients was more significant(P＜0.001),CRP and ALT decreases were more pronounced(P＜0.001),but the impact on TG was smaller.Conclusions For perioperative patients with parenteral nutrition,STG supplementation can bring significant clinical benefits.STG should be used according to the organ function and economic situation of patients.

Most patients with stroke experience obstructive sleep apnea (OSA), which has a negative impact on functional outcome and cognitive function in patients with stroke and is associated with increased mortality. Continuous positive airway pressure (CPAP) is a gold standard for treating OSA. This article reviews the effect of CPAP on functional outcome and cognitive function in stroke patients with OSA.