[Application of three-dimensional ultrasound technique in repairing dorsal foot wounds with medial sural artery perforator flaps].

Objective: To investigate the accuracy of positioning perforator of medial sural artery with three-dimensional ultrasound technique guided by a wide band linear matrix array volume transducer probe before operation, and the effectiveness of the flap design based on this in repairing the dorsal foot wounds. Methods: Between January 2019 and December 2022, 30 patients with skin and soft tissue defects of the dorsal foot were treated. There were 19 males and 11 females, with an average age of 43.9 years (range, 22-63 years). There were 12 cases of traffic accident injury, 15 cases of heavy crushing injury, and 3 cases of machine injury. The time from injury to hospitalization was 1-8 hours (mean, 3.5 hours). The wounds in size of 5 cm×3 cm to 17 cm×5 cm were thorough debrided and covered with vacuum sealing drainage dressing. Then the wounds were repaired with the medial sural artery perforator flaps after no obvious infection observed. To obtain the complete three-dimensional image, the number and position of the medial sural artery perforator branches and the position of the main blood vessels in the muscle were detected and recorded by wide band linear matrix array volume transducer probe before operation. Suitable perforating branches were selected to design the flap and guide the flap incision on this basis. The size of the perforating flap ranged from 6 cm×4 cm to 18 cm×6 cm. The sensitivity and positive predictive value were calculated by comparing preoperative exploration with intraoperative observation of perforating branches, so as to evaluate the positioning accuracy of three-dimensional ultrasound technique. The donor sites were sutured directly in 25 cases and repaired with free skin grafting in 5 cases. Results: The 60 perforating branches of medial sural artery were found before operation and 58 during operation in 30 patients. Among them, pre- and intra-operative perforations were consistent with 56. The sensitivity was 93.3% and positive predictive value was 96.6%. The intramuscular position and route of the main blood vessels were basically consistent with the pre- and intra-operative observation. All flaps survived and wounds healed by first intention. All incisions at the donor sites healed by first intention, and all skin grafts survived. All patients were follow up 9-24 months (mean, 14.7 months). The appearance, color, and texture of the flaps were good, and no obvious effect on wearing shoes and walking. At last follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind score ranged from 80 to 92, with an average of 87.5. The patient satisfaction was excellent in 29 cases and good in 1 case. Conclusion: The three-dimensional ultrasound technique guided by the wide band linear matrix array volume transducer probe can accurately locate the perforating branch of the medial sural artery, and the three-dimensional imaging is more intuitive, which can be used to guide the design and incision of the medial sural artery perforator flap.

Co-delivery of Plinabulin and Tirapazamine boosts anti-tumor efficacy by simultaneously destroying tumor blood vessels and killing tumor cells.

It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG-b-PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9 % tumor suppression rate and a 20 % cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.

Correction: Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment.

Correction for 'Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment' by Ya Liu et al., Biomater. Sci., 2024, 12, 1294-1306, https://doi.org/10.1039/D3BM01858J.

Characteristics of casein phosphopeptides in Chinese human milk and its correlation with infant growth: A cross-sectional study.

This research aimed to investigate the characteristics of casein phosphopeptides in Chinese human milk, and their potential relationship to infant growth. Using the liquid chromatography-Orbitrap-mass spectrometry technique, a total of 15 casein phosphopeptides were identified from 200 human milk samples. Also, our results indicate that casein phosphopeptides were phosphorylated with only one phosphate. The relative concentrations of casein phosphopeptides at 6 months postpartum were increased compared with milk at 2 months (FDR < 0.05). Significantly positive correlations were observed between casein phosphopeptides and infant growth, as shown by four casein phosphopeptides were positively correlated with the infants' weight-for-age Z-scores (rs range from 0.20 to 0.29), and three casein phosphopeptides were positively correlated with the infants' length-for-age Z-scores (rs range from 0.19 to 0.27). This study is the first to reveal the phosphorylated level and composition of casein phosphopeptides in Chinese human milk, and their potential relationship with infant growth.

Introducing urea into tirapazamine derivatives to enhance anticancer therapy.

Tirapazamine (TPZ) has been approved for multiple clinical trials relying on its excellent anticancer potential. However, as a typical hypoxia-activated prodrug (HAP), TPZ did not exhibit survival advantages in Phase III clinical trials when used in combination therapy due to the insufficient hypoxia levels in patients' tumors. In this study, to improve the therapeutic effects of TPZ, we first introduced urea to synthesize a series of urea-containing derivatives of TPZ. All urea-containing TPZ derivatives showed increased hypoxic cytotoxicity (9.51-30.85-fold) compared with TPZ, while maintaining hypoxic selectivity. TPZP, one of these derivatives, showed 20-fold higher cytotoxicity than TPZ while maintaining a similar hypoxic cytotoxicity ratio. To highly efficiently deliver TPZP to the tumors and reduce its side effects on healthy tissues, we further prepared TPZP into a nanodrug with fibrin-targeting ability: FT11-TPZP-NPs. CA4-NPs, a vascular disrupting agent, was used to increase the fibrin level within tumors and exacerbate tumor hypoxia. By being combined with CA4-NPs, FT11-TPZP-NPs can accumulate in the hypoxia-aggravated tumors and activate sufficiently to kill tumor cells. After a single-dose treatment, FT11-TPZP-NPs + CA4-NPs showed a high inhibition rate of 98.1% against CT26 tumor models with an initial volume of ∼480 mm3 and four out of six tumors were completely eliminated; it thereby exerted a significant antitumor effect. This study provides a new strategy for improving the therapeutic effect of TPZ and other HAPs in anticancer therapy.

Tumor Microenvironment Remodeling-Mediated Sequential Drug Delivery Potentiates Treatment Efficacy.

Toll-like receptor 7/8 agonists, such as imidazoquinolines (IMDQs), are promising for the de novo priming of antitumor immunity. However, their systemic administration is severely limited due to the off-target toxicity. Here, this work describes a sequential drug delivery strategy. The formulation is composed of two sequential modules: a tumor microenvironment remodeling nanocarrier (poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4, termed CA4-NPs) and an immunotherapy nanocarrier (apcitide peptide-decorated poly(l-glutamic acid)-graft-IMDQ-N3 conjugate, termed apcitide-PLG-IMDQ-N3 ). CA4-NPs, as a vascular disrupting agent, are utilized to remodel the tumor microenvironment for enhancing tumor coagulation and hypoxia. Subsequently, the apcitide-PLG-IMDQ-N3 could identify and target tumor coagulation through the binding of surface apcitide peptide to the GPIIb-IIIa on activated platelets. Afterward, IMDQ is activated selectively through the conversion of "-N3 " to "-NH2 " in the presence of hypoxia. The biodistribution results confirm their high tumor uptake of activated IMDQ (22.66%ID/g). By augmenting the priming and immunologic memory of tumor-specific CD8+ T cells, 4T1 and CT26 tumors with a size of ≈500 mm3 are eradicated without recurrence in mouse models.

Association between Dietary Inflammatory Index and Bone Mineral Density Changes among Pregnant Women: A Prospective Study in China.

OBJECTIVES: This study aims to examine the relationship between dietary inflammatory index (DII) and bone mineral density (BMD) changes among Chinese pregnant women, offering valuable insights for dietary guidance during pregnancy. METHODS: 289 pregnant women were enrolled in this cohort. Serum inflammatory factors and ultrasonic BMD were measured at the first, second, and the third trimesters. DII scores were calculated based on a semi-quantitative food frequency questionnaire (FFQ) and divided into tertiles. We compared the differences in inflammatory factors in serum across the tertiles of DII and changes in BMD at the second and third trimesters across the tertiles. RESULTS: The participants with higher DII scores had higher total energy intakes than those with lower DII scores. The serum level of interleukin-6 (IL-6) was significantly different across the tertiles of the DII. Women who had lower DII scores had higher T-scores and Z-scores in the BMD assessment. In the test of trends, after adjusting potential covariates, including educational level, physical activity, body mass index, and calcium, vitamin D, or multivitamin supplements, DII values were determined to be positively related to the maternal BMD lost. CONCLUSIONS: DII was positively associated with serum IL-6. Meanwhile, higher DII scores were associated with more bone mass loss in pregnant women. We recommend adhering to a lower-DII diet to preserve BMD during pregnancy.

Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment.

The rational combination of chemotherapy drugs can improve the curative effect of cancer treatment. As two early recognized tumor hallmarks, the limitless replicative potential of tumor cells is essential for the development of their malignant growth state, and sustained angiogenesis is a prerequisite to the rapid growth of tumors. Based on this, we propose a combination therapy that hinders the unlimited proliferation of tumor cells and destroys tumor blood vessels. Herein, 7-ethyl-10-hydroxycamptothecin (SN38), a typical topoisomerase I inhibitor, was bonded to poly(L-glutamic acid) (PLG) to prepare the nanodrug SN38-NPs, which hinders the unlimited proliferation of tumor cells. A poly(L-glutamic acid)-combretastatin A4 conjugate (CA4-NPs), a representative vascular disrupting agent (VDA), was used to selectively disrupt the tumor blood vessels, cutting off the necessary nutrients and oxygen for the proliferation of tumor cells. In the 4T1 tumor model with an initial volume of about 400 mm3, the combined treatment of SN38-NPs and CA4-NPs showed an excellent cancer treatment effect with a tumor suppression rate of 94.3% and a synergistic interaction (Q = 1.25). Our study provides a new combination therapy approach for chemotherapy, with the hope of further improving the curative effect of anti-cancer therapy.

[A prospective study of super-thin anterolateral thigh flap harvesting assisted by high-frequency color Doppler ultrasound in detecting perforators in deep adipose layers].

Objective: To investigate the clinical application of high-frequency color Doppler ultrasound (HFCDU) in detecting perforators in the deep adipose layers for harvesting super-thin anterolateral thigh flap (ALTF). Methods: Between August 2019 and January 2023, 45 patients (46 sides) with skin and soft tissue defects in the foot and ankle were treated, including 29 males and 16 females, aged from 22 to 62 years, with an average of 46.7 years. The body mass index ranged from 19.6 to 36.2 kg/m 2, with an average of 23.62 kg/m 2. The causes of injury included traffic accident injury in 15 cases, heavy object crush injury in 20 cases, mechanical injury in 8 cases, heat crush injury in 1 case, and chronic infection in 1 case. There were 20 cases on the left side, 24 cases on the right side, and 1 case on both sides. After thorough debridement, the wound size ranged from 5 cm×4 cm to 17 cm×11 cm. All patients underwent free super-thin ALTF transplantation repair. HFCDU was used to detect the location of the perforators piercing the deep and superficial fascia, as well as the direction and branches of the perforators within the deep adipose layers before operation. According to the preoperative HFCDU findings, the dimensions of the super-thin ALTF ranged from 6 cm×4 cm to 18 cm×12 cm. The donor sites of the flaps were directly sutured. Results: A total of 55 perforators were detected by HFCDU before operation, but 1 was not found during operation. During operation, a total of 56 perforators were found, and 2 perforators were not detected by HFCDU. The positive predictive value of HFCDU for identifying perforator vessels was 98.2%, and the sensitivity was 96.4%. Among the 54 perforators accurately located by HFCDU, the orientation of the perforators in the deep adipose layers was confirmed during operation. There were 21 perforators (38.9%) traveled laterally and inferiorly, 12 (22.2%) traveled medially and inferiorly, 14 (25.9%) traveled laterally and superiorly, 5 (9.3%) traveled medially and superiorly, and 2 (3.7%) ran almost vertically to the body surface. Among the 54 perforators accurately located by HFCDU, 35 were identified as type 1 perforators and 12 as type 2 perforators (HFCDU misidentified 7 type 2 perforators as type 1 perforators). The sensitivity of HFCDU in identifying type 1 perforators was 100%, with a positive predictive value of 83.3%. For type 2 perforators, the sensitivity was 63.2%, and the positive predictive value was 100%. The surgeries were successfully completed. The super-thin ALTF had a thickness ranging from 2 to 6 mm, with an average of 3.56 mm. All super-thin ALTF survived, however, 1 flap experienced a venous crisis at 1 day after operation, but it survived after emergency exploration and re-anastomosis of the veins; 1 flap developed venous crisis at 3 days after operation but survived after bleeding with several small incisions; 3 flaps had necrosis at the distal edge of the epidermis, which healed after undergoing dressing changes. All 45 patients were followed up 6-18 months (mean, 13.6 months). Three flaps required secondary defatting procedures, while the rest had the appropriate thickness, and the overall appearance was satisfactory. Conclusion: Preoperative application of HFCDU to detect the perforator in the deep adipose layers can improve the success and safety of the procedure by facilitating the harvest of super-thin ALTF.

An ultrafast and self-powered MoSxSe2-x/Si photodetector with high light-trapping structures and a SiOx interface layer.

MoSxSe2-x nanofilms, as a typical metal dichalcogenide, have attracted great interest, due to their adjustable bandgap and distinctive electronic and optical properties. However, the inherent bandgap of MoSxSe2-x and the strong interface recombination impede the actualization of a high-sensitivity photodetector (PD). Few-layer MoSxSe2-x nanofilms were prepared with vertically orientation at 450 °C, which would be a less restrictive choice of substrates. Herein, a self-powered MoSxSe2-x/SiOx/Si photodetector was fabricated which exhibits unprecedented performance with excellent reproducibility and stability from 405 nm to 980 nm, a high responsivity (0.450 A W-1), normalized detectivity (4.968 × 1012 Jones) and ultrafast photoresponse (τr = 1.20 µs, τf = 4.92 µs) at zero bias under 980 nm incident laser illumination with a density of 200 µW cm-2. Significantly, the self-powered PD is capable of detecting ultraweak IR signals below 200 µW cm-2 with high on-off ratios. More importantly, an oxidized atomic layer is generated through the wet oxidation in the Piranha solution. The PD can work well at high frequencies even at 100 kHz, which shows its potential application in high-frequency photoelectric devices and health monitors. Summing up, this work not only suggests that an ultrathin SiOx interface layer can reduce carrier recombination via simple interface engineering, but also proposes a novel strategy for the preparation of high-performance and low-cost optoelectronic devices.

Evaluating the Clinical Efficacy of Teriparatide and Denosumab Combination Therapy in Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aims to assess the clinical effectiveness of the combination therapy involving Teriparatide (TPTD) and Denosumab (DEN) in managing postmenopausal osteoporosis (PMO). The findings provide valuable insights into clinical treatment decisions. Methods: We conducted a comprehensive search of PubMed, the Cochrane Library, Embase, and other relevant databases to gather literature concerning the treatment of PMO with TPTD and DEN. After a thorough screening, we selected and analyzed the final literature set. Information relevant to the study was extracted, and a quality assessment was carried out. The meta-analysis utilized RevMan 5.3 software to evaluate the impact of DEN combined with TPTD on parameters such as bone mineral density (BMD), tartrate-resistant acid phosphatase-5b (TRACP-5b), fracture incidence, and adverse reactions in PMO patients. Results: After the screening process, a total of 513 patients were studied across 8 studies. Among these, 259 patients received treatment involving DEN combined with TPTD (the research group), while 254 patients were subjected to different treatment regimens (the control group). As per the Cochrane Handbook's quality assessment, all included literature exhibited high overall quality. The meta-analysis demonstrated that the research group exhibited significantly higher BMD than the control group, lower TRACP-5b levels and fracture incidence (P < .05). However, the two groups had no evident difference in adverse reaction incidence (P > .05). Conclusions: The combined treatment of DEN and TPTD exhibits notable efficacy in managing PMO, warranting its promotion and use in clinical practice.

Advances in Roles of Salicylic Acid in Plant Tolerance Responses to Biotic and Abiotic Stresses.

A multitude of biotic and abiotic stress factors do harm to plants by bringing about diseases and inhibiting normal growth and development. As a pivotal signaling molecule, salicylic acid (SA) plays crucial roles in plant tolerance responses to both biotic and abiotic stresses, thereby maintaining plant normal growth and improving yields under stress. In view of this, this paper mainly discusses the role of SA in both biotic and abiotic stresses of plants. SA regulates the expression of genes involved in defense signaling pathways, thus enhancing plant immunity. In addition, SA mitigates the negative effects of abiotic stresses, and acts as a signaling molecule to induce the expression of stress-responsive genes and the synthesis of stress-related proteins. In addition, SA also improves certain yield-related photosynthetic indexes, thereby enhancing crop yield under stress. On the other hand, SA acts with other signaling molecules, such as jasmonic acid (JA), auxin, ethylene (ETH), and so on, in regulating plant growth and improving tolerance under stress. This paper reviews recent advances in SA's roles in plant stress tolerance, so as to provide theoretical references for further studies concerning the decryption of molecular mechanisms for SA's roles and the improvement of crop management under stress.

The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice.

Resveratrol, curcumin, and quercetin are the secondary metabolites from medicinal food homology plants, that have been proven their potency in cancer treatment. However, the antitumor effect of a single component is weak. So, herein, we designed an antitumor compound named RCQ composed of resveratrol, curcumin, and quercetin. This study examined the effect on tumorigenesis and development of 4T1 breast cancer-bearing mice following administering RCQ by intragastric administration. RCQ increased the recruitment of T cells and reduced the accumulation of neutrophils and macrophages in the tumor microenvironment. Meanwhile, RCQ suppressed the development of tumor-infiltrating lymphocytes into immunosuppressive cell subpopulations, including CD4+ T cells to T helper Type 2 type (Th2), tumor-associated neutrophils (TANs) to the N2 TANs, and tumor-associated macrophages (TAMs) cells to M2 TAMs. RCQ reversed the predominance of immunosuppressive infiltrating cells in the tumor microenvironment and tipped the immune balance toward an immune activation state. In vitro the study showed that RCQ significantly increased reactive oxygen species (ROS), reduce mitochondrial membrane potentials in cancer cells, and modulate pro-apoptotic Bcl-2 family members. In conclusion, RCQ can promote the ROS apoptosis mechanism of tumor cells and alleviate immunosuppression of the tumor microenvironment to enhance the anti-tumor effect.

Development and Validation of Nutrition Literacy Assessment Instrument for Chinese Lactating Women: A Preliminary Study.

This study focused on the development and validation of a nutrition literacy assessment instrument for Chinese lactating women (NLAI-L). A comprehensive literature review and group discussion by experts in relevant fields were adopted to determine the dimension, topics and questions of NLAI-L. Content validity was evaluated by a panel of experts. The exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were used to evaluate the construct validity. Cronbach's α and split-half reliability were applied to examine the reliability of NLAI-L. The final NLAI-L consisted of 38 questions covering three dimensions: knowledge, behavior and skill. The EFA revealed four sub-domains for knowledge, one sub-domain for behavior and four sub-domains for skill. The results showed that NLAI-L had satisfactory content validity (CVI = 0.98, CVR = 0.96), good reliability (Cronbach's α coefficient = 0.84) and acceptable construct validity (χ2/df = 2.28, GFI = 2.81, AGFI = 0.79, RMSEA = 0.057). In the application part, the average NL score was 46.0 ± 9.3. In multivariate linear regression, education level, age, postnatal period and occupation were the potential influencing factors of NL for Chinese lactating women. The study established an effective and reliable assessment instrument for Chinese lactating women (NLAI-L) through qualitative and quantitative methods. The establishment of NLAI-L will provide an effective tool for exploring the role of NL in health or disease and provide a basis for the formulation of targeted nutrition interventions.

Effect of Thoracic Epidural Anesthesia on Perioperative Neutrophil Extracellular Trapping Markers in Patients Undergoing Anesthesia and Surgery for Colorectal Cancer: A Randomized, Controlled Trial.

BACKGROUND: Neutrophil extracellular trapping (NETosis) is an immunologic mechanism strongly linked with increased metastatic risk in colorectal cancer. The authors hypothesized that patients who received propofol-epidural anesthesia (PEA) would exhibit decreases in the expression of serum neutrophil myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit) levels compared with patients who received general anesthesia (GA). METHODS: Colorectal cancer surgery patients were randomly assigned to the PEA (n = 30) or GA (n = 30) group. Serum MPO, H3Cit, and metalloproteinase-9 (MMP-9) levels before surgery and 24 h after surgery were measured, and visual analogue scale (VAS) scores were recorded. RESULTS: The patients who received PEA showed decreases in MPO (28.06 ± 11.23 vs 20.54 ± 7.29 ng/ ml; P = 0.004) and H3Cit [3.22 ± 0.86 vs 2.73 ± 0.94 ng/ ml; P = 0.042) 24 h after surgery compared with the patients subjected to GA. In addition, there was no difference in MMP-9 levels (75.98 ± 26.9 vs 73.45 ± 28.4 ng/ ml; P = 0.726). The visual analogue scale scores 2 h and 24 h after operation were significantly lower in PEA group (P < 0.05). The number of postoperative analgesia pump pressings and sufentanil consumptions within 48 h after surgery were significantly lower in the PEA group (P < 0.001). CONCLUSIONS: Propofol-epidural anesthesia reduces the expression of NETosis (MPO and H3Cit) in serum during colorectal cancer surgery. CLINICAL TRIAL REGISTRATION: ChiCTR2200066708 ( www.chictr.org.cn ).

Comparative analysis of oligosaccharides in the milk of human and animals by using LC-QE-HF-MS.

The complex oligosaccharides (OS) in different milk are more difficult to detect and complicated to analyze as their enormous structural complexity. UPLC-QE-HF-MS was supposed to be a highly effective method for OS identification. In present study, 70 human milk oligosaccharides (HMOs), 14 bovine milk oligosaccharides (BMOs), 23 goat milk oligosaccharides (GMOs) and 24 rat milk oligosaccharides (RMOs) were detected by using UPLC-QE-HF-MS, respectively. There were highly differences in number and composition between the four milk OS. 14 neutral and 3 acidic OS were firstly found in rat milk. The composition and abundances of RMOs were might more similar to that of HMOs, comparing with BMOs and GMOs. The similarity between HMOs and RMOs might provide theoretical basis for better application of rats in biological/biomedical studies of HMOs as models. The BMOs and GMOs were expected to be suitable for applications in medical and functional foods as a promising bioactive molecular.

Nutrition and Metabolism in the First 1000 Days of Life.

The first 1000 days of life are a critical window period for rapid growth and development during which individuals are more sensitive to the stimulation of environmental factors [...].