Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

It was a retrospective study. The propensity score matching was applied to divide the type 2 diabetes mellitus (T2DM) patients who have underwent percutaneous coronary intervention (PCI) into two groups: short-term (<4 weeks) sodium-glucose cotransporter 2 inhibitor (SGLT2i) group (213 patients) and control group (213 patients). The occurrence of contrast-induced acute kidney injury (CIAKI) after PCI was compared between the two groups. The results showed that the incidence of CIAKI in the SGLT2i group was not significantly different from the control group [10.8% (23/213) vs. 7.5% (16/213), χ2=1.383, P=0.313]. The incidence of CIAKI in patients with SGLT2i application time <1 week was higher than that in control patients, but the difference was not statistically significant [13.00% (16/123) vs. 7.5% (16/213), χ2=2.734, P=0.122]. Multivariate logistic regression analysis showed that short-term (<4 weeks) use of SGLT2i would not increase the risk of CIAKI after PCI in T2DM patients ( OR=0.507, 95% CI 0.238-1.077, P=0.077). Short-term application of SGLT2i before PCI may not increase the risk of CIAKI, but it is advisable to avoid initiating the application of SGLT2i before PCI as much as possible.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

OBJECTIVE: To investigate the anthropometric parameters that can accurately predict the diameter of the hamstring tendon graft, and to examine the correlation between disease etiology, duration, and graft diameter. METHODS: A retrospective analysis was conducted on data from 166 patients who underwent anterior cruciate ligament reconstruction using hamstring tendon autografts (semitendinosus and gracilis tendon) between January 2013 and December 2023. The cohort conprised 135 males and 31 females;the age ranged from 14 to 62 years old with an average of (28.87±10.46) years old. Pearson correlation coefficients, partial correlation coefficients, and stepwise multiple linear regression analysis were utilized to elucidate the relationship between the outcome variable (diameter of hamstring tendon grafts) and predictive variables (e.g., height). RESULTS: Correlation analysis revealed significant associations between the diameter of hamstring tendon grafts and height (r=0.379, P<0.001), weight (r=0.225, P=0.002), male gender (r=0.302, P<0.001), age(r=-0.218, P=0.002), and sports injury etiology (r=0.167, P=0.016). No significant correlations were found with surgical side, body mass index (BMI), or injury duration (P>0.05). Stepwise multiple linear regression analysis using a backward elimination method indicated that height was the sole significant predictive variable (R²=0.144, P<0.001), with the optimal predictive equation being:Graft size =2.636+0.029×Height (cm). Partial correlation analysis, after controlling for height, showed no significant association between age, gender, weight, and injury etiology with graft diameter. CONCLUSION Height is an effective predictive factor for the diameter of autologous hamstring tendon grafts. Factors such as gender, age, surgical side, body weight, and BMI are not influential to the diameter of the hamstring tendon grafts. Under the condition of the same height, there is no significant difference in the influence of these factors on the graft diameter. Preoperative physical activity level and the duration of injury do not significantly affect the diameter of the hamstring tendon grafts obtained during surgery. It is recommended to use the formula 'Graft Diameter=2.636 + 0.029 × Height (cm)' for preoperative prediction.
Humans ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Adolescent ; Young Adult ; Transplantation, Autologous ; Anthropometry ; Anterior Cruciate Ligament Reconstruction ; Tendons/anatomy & histology* ; Autografts ; Hamstring Tendons/transplantation* ; Quadriceps Muscle/surgery*

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.