ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective:To explore the early diagnostic value of combined detection of serum chitinase protein 40 (YKL-40), galectin-3 (Gal-3), and regulated upon activation normal T cell expressed and secreted (RANTES) for refractory mycoplasma pneumoniae pneumonia (RMPP) in children.Methods:One hundred and twenty-six children with RMPP (RMPP group), 126 children with global mycoplasma pneumoniae pneumonia (GMPP) (GMPP group), and 126 healthy children who underwent physical check up (control group) in the Affiliated Hospital of Jining Medical College from June 2022 to June 2024 were retrospectively selected. The serum levels of YKL-40, Gal-3 and RANTES were compared. Multivariate Logistic regression was used to analyze the independent influencing factors of RMPP. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40, Gal-3 and RANTES levels for RMPP.Results:Compared with the control group, the serum YKL-40, Gal-3 and RANTES levels in the RMPP and GMPP groups were obviously higher: (42.19 ± 4.94) and (37.68 ± 4.25) μg/L vs. (26.73 ± 3.31) μg/L, (12.24 ± 2.89) and (8.87 ± 2.56) ng/L vs. (3.92 ± 1.27) ng/L, (33.82 ± 3.86) and (29.28 ± 3.72) μg/L vs. (21.34 ± 2.79) μg/L, with statistical significance ( P<0.05). Compared with the GMPP group, the serum YKL-40, Gal-3 and RANTES levels in the RMPP group were obviously higher ( P<0.05). Compared with the GMPP group, there was no statistically obvious difference in age, gender, body weight, duration of fever and atelectasis in the RMPP group ( P>0.05), however, the levels of C-reactive protein (CRP), procalcitonin (PCT), and the proportions of pleural effusion and lung consolidation were obviously higher in the RMPP group: (22.45 ± 4.21) mg/L vs. (18.69 ± 3.56) mg/L, (0.18 ± 0.04) μg/L vs. (0.15 ± 0.03) μg/L, 31.75% (40/126) vs. 17.46% (22/126), 38.89% (49/126) vs. 25.40% (32/126), P<0.05. CRP, PCT, pleural effusion, pulmonary consolidation, YKL-40, Gal-3 and RANTES were all independent influencing factors of RMPP ( P<0.05). The areas under the curve (AUC) of serum YKL-40, Gal-3 and RANTES levels for diagnosing RMPP in children were 0.769, 0.833 and 0.825, respectively. The AUC of the combined diagnosis of YKL-40, Gal-3 and RANTES was 0.923, which was obviously higher than that of the single indicator diagnosis ( Z = 5.373, 3.677 and 4.191; P<0.01). The sensitivity of the three combined diagnosis was 73.81%, and the specificity was 92.86%. Conclusions:Serum YKL-40, Gal-3 and RANTES levels are obviously elevated in patients with RMPP, and all of which are influencing factors of RMPP. The combination of the three has high diagnostic value for RMPP.

Non-small cell lung cancer(NSCLC)continues to exhibit a high incidence and mortality worldwide,posing a serious threat to human health.In recent years,the rapid advancement of immunotherapy has profoundly reshaped the therapeutic paradigm for NSCLC,particularly by improving long-term outcomes in the perioperative period.However,with its increasingly widespread clinical use during this period,several critical issues have emerged,including the precise identification of patients most likely to benefit,optimization of therapeutic strategies,evaluation of pathological value,formulation of adjuvant therapy strategies for patients with complete pathological response after surgery,and the management of immune-related adverse events.This review will systematically discuss these key challenges and aims to provide insights that may facilitate the standardized application of perioperative immunotherapy in NSCLC.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective To explore the clinical effect of quality control circle(QCC)activities on the prevention of postoperative deep vein thrombosis(DVT)in inpatients in military hospitals.Methods A total of 318 patients who were diagnosed and treated in The First Affiliated Hospital of Air Force Medical University from January to December 2021 and 40 medical staff were enrolled in this study.Routine care was performed in 158 patients from January to June 2021,and QCC care was implemented in 160 patients from July to December 2021.The awareness of DVT prevention in medical staff and patients(or their famiy members)before and after QCC activities,lower limb DVT preventive measures taken by medical staff,and the occurrence of DVT were compared.Results The scores of the cause,clinical manifestations,nursing measures and preventive measures of DVT after QCC activities were significantly higher than those before QCC activities in both medical staff and patients(or their families)(P<0.05).The overall implementation rate of preventing lower limb DVT after QCC activities was significantly higher than that before QCC activities(94.14%vs.46.20%,P<0.05).The incidence of DVT after QCC activities was significantly lower than that before QCC activities(0.62%vs.5.06%,P<0.05).Conclusion Implementing QCC activities can improve the cognitive ability of military medical staff and patients(or family members)in DVT prevention,increase the implementation rate of DVT prevention measures,and reduce the incidence of DVT.

Non-small cell lung cancer(NSCLC)continues to exhibit a high incidence and mortality worldwide,posing a serious threat to human health.In recent years,the rapid advancement of immunotherapy has profoundly reshaped the therapeutic paradigm for NSCLC,particularly by improving long-term outcomes in the perioperative period.However,with its increasingly widespread clinical use during this period,several critical issues have emerged,including the precise identification of patients most likely to benefit,optimization of therapeutic strategies,evaluation of pathological value,formulation of adjuvant therapy strategies for patients with complete pathological response after surgery,and the management of immune-related adverse events.This review will systematically discuss these key challenges and aims to provide insights that may facilitate the standardized application of perioperative immunotherapy in NSCLC.

Objective To quantify the mean fat fraction(FF)values of hip abductor muscles using the MR least squares estimation method of iterative water-fat separation(IDEAL-IQ)technique and to analyze the correlation between muscle fat infiltration and cartilage damage in hip osteoarthritis(HOA),age and gender.Methods Ninety-five patients with clinical symptoms of hip joint(HOA group)and volunteers(control group)underwent MRI conventional sequence and IDEAL-IQ sequence scans of the hip joint were selected.Hip cartilage damage was graded based on conventional MRI sequences(mild HOA group and severe HOA group),and the FF values of hip abductor muscles were measured for each group.ANOVA analysis and Pearson correlation tests were used to compare the differences between the groups and correlation analyses were performed.Results The FF values of hip abductor muscles in the mild HOA group and severe HOA group were significantly higher than those in the control group,with statistically significant differences(P＜0.05).There were correlations between the FF values of hip abductor muscles and the degree of HOA cartilage damage,age and gender(r=0.677,0.566,0.311).Conclusion The IDEAL-IQ technique can be used for quantitative research on muscle fat infiltration,and fat infiltration in hip abductor muscles is an important risk factor for HOA cartilage damage.

Objective:To explore the early diagnostic value of combined detection of serum chitinase protein 40 (YKL-40), galectin-3 (Gal-3), and regulated upon activation normal T cell expressed and secreted (RANTES) for refractory mycoplasma pneumoniae pneumonia (RMPP) in children.Methods:One hundred and twenty-six children with RMPP (RMPP group), 126 children with global mycoplasma pneumoniae pneumonia (GMPP) (GMPP group), and 126 healthy children who underwent physical check up (control group) in the Affiliated Hospital of Jining Medical College from June 2022 to June 2024 were retrospectively selected. The serum levels of YKL-40, Gal-3 and RANTES were compared. Multivariate Logistic regression was used to analyze the independent influencing factors of RMPP. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40, Gal-3 and RANTES levels for RMPP.Results:Compared with the control group, the serum YKL-40, Gal-3 and RANTES levels in the RMPP and GMPP groups were obviously higher: (42.19 ± 4.94) and (37.68 ± 4.25) μg/L vs. (26.73 ± 3.31) μg/L, (12.24 ± 2.89) and (8.87 ± 2.56) ng/L vs. (3.92 ± 1.27) ng/L, (33.82 ± 3.86) and (29.28 ± 3.72) μg/L vs. (21.34 ± 2.79) μg/L, with statistical significance ( P<0.05). Compared with the GMPP group, the serum YKL-40, Gal-3 and RANTES levels in the RMPP group were obviously higher ( P<0.05). Compared with the GMPP group, there was no statistically obvious difference in age, gender, body weight, duration of fever and atelectasis in the RMPP group ( P>0.05), however, the levels of C-reactive protein (CRP), procalcitonin (PCT), and the proportions of pleural effusion and lung consolidation were obviously higher in the RMPP group: (22.45 ± 4.21) mg/L vs. (18.69 ± 3.56) mg/L, (0.18 ± 0.04) μg/L vs. (0.15 ± 0.03) μg/L, 31.75% (40/126) vs. 17.46% (22/126), 38.89% (49/126) vs. 25.40% (32/126), P<0.05. CRP, PCT, pleural effusion, pulmonary consolidation, YKL-40, Gal-3 and RANTES were all independent influencing factors of RMPP ( P<0.05). The areas under the curve (AUC) of serum YKL-40, Gal-3 and RANTES levels for diagnosing RMPP in children were 0.769, 0.833 and 0.825, respectively. The AUC of the combined diagnosis of YKL-40, Gal-3 and RANTES was 0.923, which was obviously higher than that of the single indicator diagnosis ( Z = 5.373, 3.677 and 4.191; P<0.01). The sensitivity of the three combined diagnosis was 73.81%, and the specificity was 92.86%. Conclusions:Serum YKL-40, Gal-3 and RANTES levels are obviously elevated in patients with RMPP, and all of which are influencing factors of RMPP. The combination of the three has high diagnostic value for RMPP.

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions