AIM To investigate the effects of Wenyang Jiedu Tongluo Recipe(WYJDTLR)on macrophage recruitment and polarization function in a mouse model of diabetic kidney disease(DKD).METHODS 50 db/db mice were randomly divided into the model group,the valsartan group(10.29 mg/kg)and the high-dose,medium-dose and low-dose WYJDTLR groups(26.52,13.26 and 6.63 g/kg),with 10 mice in each group,in contrast to another 10 db/m mice of the blank group.After 8 weeks of administration,the mice had their levels of fasting blood glucose,24-hour urinary protein quantity(24h-UTP),serum creatinine(Scr)and blood urea nitrogen(BUN)observed;their morphological changes of renal tissues observed by HE staining;their degree of renal glycogen deposition observed by PAS staining;their degree of renal fibrosis observed by Masson staining;their levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1 β in renal tissue detected by ELISA;their renal protein expressions of VCAM-1 and ICAM-1 detected by IHC and Western blot;and their renal expressions of CD86 and CD206 detected by IF.RESULTS Compared with the model group,the WYJDTLR groups displayed decreased levels of fasting blood glucose,24h-UTP,Scr and BUN(P＜0.05,P＜0.01);improved degree of glomerular hypertrophy,mild proliferation of mesangial cells,dilatation of renal tubular,vacuolar degeneration of renal tubular epithelial cells,deposition of glomerular glycogen,and fibrosis of renal tissues(P＜0.01);decreased levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1β in renal tissue(P＜0.05,P＜0.01);decreased renal protein expressions of VCAM-1 and ICAM-1(P＜0.05,P＜0.01),thus reduced the recruitment of macrophages to the kidney;decreased renal CD86 protein expression(P＜0.01);and increased CD206 protein expression(P＜0.01),thus inhibited M1-type polarization of macrophages and promoted M2-type polarization of macrophages.CONCLUSION WYJDTLR can delay the DKD progression in mice by reducing the occurrence of inflammatory reactions through reducing the level of macrophage recruitment factor,inhibiting the M1-type polarization,and promoting the M2-type polarization.

Objective To compare the smile incision combined with indirect reduction technique with traditional ORIF technique and systematically evaluate the advantages of this innovative surgical method in terms of functional recovery and postoperative cosmetic effects.Methods A total of 60 patients with midshaft clavicle fractures were enrolled between October 2022 and August 2024.The patients were randomly assigned to either ORIF group(open reduction and internal fixation,n=30)or MIPPO group(MIPPO combined with smile incision,n=30).Outcomes assessed included surgical trauma,functional recovery,and cosmetic outcomes.Results The MIPPO group exhibited significantly reduced intraoperative blood loss[(32.9±7.6)mL vs.(90.2±14.0)mL,P＜0.05],shorter incision length[(3.0±0.5)cm vs.(8.5±1.2)cm,P＜0.05],and reduced operative time compared to the ORIF group.Functional recovery indicators such as bone healing time[(10.1±1.7)weeks vs.(12.8±2.0)weeks,P＜0.05],initial and complete self-care time,and weight-bearing recovery were all significantly improved in the MIPPO group.The Constant-Murley score was higher in the MIPPO group(91.5±5.1 vs.82.4±6.0,P＜0.05).Cosmetic outcomes also favored the MIPPO group,with a superior SBSES score(9.2±0.4 vs.3.0±0.7,P＜0.05)and better results in scar visibility,pigmentation,thickness,and elasticity.Conclusion The smile incision combined with indirect reduction technique significantly reduces surgical trauma,accelerates postoperative recovery,and provides substantially better cosmetic outcomes compared to conventional methods,making it particularly suitable for patients with high aesthetic expectations.

OBJECTIVE To systematically evaluate the efficacy and safety of different chemotherapy combination regimens for first-line treatment of metastatic colorectal cancer （mCRC）. METHODS PubMed， Cochrane Library， Embase and Web of Science were electronically searched to collect randomized controlled clinical trial （RCT） on first-line treatment for mCRC from January 1， 2000 to February 16， 2025. Two reviewers independently screened literature， extracted data and assessed the risk of bias of the included studies. Network meta-analysis was performed by using R4.4.3 and Stata 17.0 software. RESULTS A total of 28 RCTs， involving 16 intervention measures， were included. In terms of prolonging progression-free survival （PFS） and overall survival （OS）， FOLFOX （5-fluorouracil+oxaliplatin+calcium folinate regimen）+cetuximab had the highest probability of ranking first. In terms of improving objective response rate （ORR）， FOLFOXIRI （5-fluorouracil+oxaliplatin+irinotecan+calcium folinate regimen）+ bevacizumab and FOLFOX+bevacizumab+nivolumab had the highest probability of ranking first； in terms of the incidence of grade 3 or higher adverse reactions， FOLFOXIRI+panitumumab had the highest probability of ranking first； in subgroup analysis of KRAS wild-type patients， FOLFIRI （5-fluorouracil+irinotecan+calcium folinate regimen）+panitumumab and FOLFIRI+bevacizumab had the highest probability of ranking first in terms of prolonging PFS and OS， respectively； in terms of ORR， FOLFOXIRI+ cetuximab had the highest probability of ranking first. CONCLUSIONS In first-line treatment for mCRC， FOLFOX combined with targeted therapy has advantages in terms of efficacy and safety. However， individualized treatment strategies should be formulated based on the KRAS gene status and tumor location of patients.

Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

Postoperative nausea and vomiting (PONV) are common complications that mainly occur within 24 h after orthognathic surgery. The incidence of nausea and vomiting after orthognathic surgery remains high and is a difficult problem for patients and surgeons. These complications not only affect wound healing and increase the risk of postoperative bleeding. Vomit and blood may also cause nausea and vomiting, which results in a vicious cycle. Frequent nausea and vomiting are a painful experience and more serious than postoperative pain. They are one of the main reasons for postoperative infection, delayed discharge, and increased hospitalization costs and affect patient satisfaction. In this review, the author combined literature review and clinical experience and summarized and analyzed the causes of orthognathic nausea and vomiting and prevention and treatment strategies to improving the related clinical process.
Humans ; Postoperative Nausea and Vomiting/etiology* ; Orthognathic Surgical Procedures/adverse effects*

Objective To compare the smile incision combined with indirect reduction technique with traditional ORIF technique and systematically evaluate the advantages of this innovative surgical method in terms of functional recovery and postoperative cosmetic effects.Methods A total of 60 patients with midshaft clavicle fractures were enrolled between October 2022 and August 2024.The patients were randomly assigned to either ORIF group(open reduction and internal fixation,n=30)or MIPPO group(MIPPO combined with smile incision,n=30).Outcomes assessed included surgical trauma,functional recovery,and cosmetic outcomes.Results The MIPPO group exhibited significantly reduced intraoperative blood loss[(32.9±7.6)mL vs.(90.2±14.0)mL,P＜0.05],shorter incision length[(3.0±0.5)cm vs.(8.5±1.2)cm,P＜0.05],and reduced operative time compared to the ORIF group.Functional recovery indicators such as bone healing time[(10.1±1.7)weeks vs.(12.8±2.0)weeks,P＜0.05],initial and complete self-care time,and weight-bearing recovery were all significantly improved in the MIPPO group.The Constant-Murley score was higher in the MIPPO group(91.5±5.1 vs.82.4±6.0,P＜0.05).Cosmetic outcomes also favored the MIPPO group,with a superior SBSES score(9.2±0.4 vs.3.0±0.7,P＜0.05)and better results in scar visibility,pigmentation,thickness,and elasticity.Conclusion The smile incision combined with indirect reduction technique significantly reduces surgical trauma,accelerates postoperative recovery,and provides substantially better cosmetic outcomes compared to conventional methods,making it particularly suitable for patients with high aesthetic expectations.

Objective To evaluate the diagnostic value of black blood computed tomography(BBCT)in vulnerable plaques at the carotid bifurcation.Methods The imaging data of 73 patients with suspected carotid atherosclerosis were retrospectively analyzed.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of conventional computed tomography angiography(CTA)ima-ges and BBCT images were compared by paired sample t-test.The 5-level scoring method was applied to evaluate the image quality subjectively,and the Friedman test was used to compare the differences in the subjective evaluation of image quality among the groups.Taking high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)as the gold standard,the diagnostic value between BBCT and conventional CTA was compared,and the consistency of BBCT and HRMR-VWI in the evaluation of vulnerable plaques was calculated.Results The standard deviation(SD)value of BBCT images was lower than that of conventional three-phase CTA images,indicating better quality of BBCT images(P＜0.001).The mean CT value and CNRplaque-lumen of non-calcified plaques were higher in BBCT images than those in conventional three-phase CTA images,suggesting that BBCT had a higher contrast with sur-rounding tissues and could better display the fine structure of non-calcified plaques(P＜0.001).BBCT images achieved the highest scores in the subjective evaluation of image quality(P＜0.001).Compared with conventional CTA images,BBCT had higher sensi-tivity(88.2％vs 29.4％)and accuracy(90.9％vs 54.5％)in identifying vulnerable plaques(P＜0.001).The Kappa value between BBCT and HRMR-VWI was 0.813,showed good consistency.Conclusion The image quality of neck BBCT is superior to that of conventional CTA.BBCT has a better effect than conventional CTA in identifying vulnerable plaques at the carotid bifurcation,which is comparable to HRMR-VWI.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.