BACKGROUND:The repair process of skin trauma is complex and susceptible to infection,easy to lead to poor healing,is the current difficulty and hot spot in wound repair research,and has received extensive attention in the fields of traditional Chinese medicine and tissue engineering. OBJECTIVE:To investigate the effect of moxibustion and reduced graphene oxide/cerium oxide nanocomposite on promoting the healing of infectious wounds. METHODS:(1)Reduced graphene oxide/cerium dioxide nanocomposites with mass ratios of 2:1,1:1 and 1:2 were synthesized by hydrothermal method.The resulting composites were recorded as G2C1,G1C1 and G1C2,respectively.The photothermal properties,cytotoxicity and antibacterial properties of the three kinds of materials were tested.After taking moxa sticks,three kinds of moxibustion distances were set(3.0-3.5 cm,recorded as moxibustion 1;2.5-3.0 cm,recorded as moxibustion 2;2.0-2.5 cm,recorded as moxibustion 3).Moxibustion was applied to the surface of human skin for 10 minutes to detect the photothermal properties.The antibacterial properties of moxibustion were tested at three different distance intervals.Simultaneously,the back body surface infrared imaging of rats with different mass concentrations of G1C1 material,moxibustion(three kinds of moxibustion distances)and moxibustion 2+G1C1 material was detected.(2)Sixty male Sprague-Dawley rats were selected to model the wound of Staphylococcus aureus infection.48 hours later,they were randomly divided into 10 groups with 6 rats in each group:control group(did not receive any treatment),mupirocin group,moxibustion 2+G1C1 group,moxibustion 1 group,moxibustion 2 group,moxibustion 3 group and 60,80,100,and 120 μg/mL G1C1 groups(The G1C1 group was given 808 nm near-infrared laser irradiation for 10 min/time,and the G1C1 suspension was loaded on the wound surface before each treatment.Each group of moxibustion underwent in-situ suspension moxibustion,and the intervention time was 10 min/time.Moxibustion 2+G1C1 group was loaded with G1C1 suspension on the wound surface before each treatment,and moxibustion was suspended in situ with moxa strips,and the intervention time was 10 min/time).The frequency of treatment was 2 days once.Wound healing,wound colony count and repair were detected after 7 days of intervention. RESULTS AND CONCLUSION:(1)The three kinds of reduced graphene oxide/cerium dioxide nanocomposites had good photothermal properties,and the higher the mass concentration of the composites,the better the photothermal properties.The temperature of the moxibustion 2 group reached 47.6 ℃for 10 minutes without causing thermal damage,which was more suitable for animal experiments.The results of co-culture with NIH-3T3 cells exhibited that 60,80,and 100 μg/mL G1C1 had good biocompatibility.The results of a co-culture experiment with Staphylococcus aureus suspension displayed that G2C1,G1C1 and G1C2 had good antibacterial activity,among which G1C1 group demonstrated excellent antibacterial performance,and the antibacterial rate reached 100％when its mass concentration was 80 μg/mL.60-120 μg/mL G1C1 could effectively remove Staphylococcus aureus biofilm,and the higher the material mass concentration,the better the removal effect.Moxibustion could also effectively remove Staphylococcus aureus biofilm,and the closer the moxibustion was,the better the removal effect.(2)Compared with the control group,the wound area of the mupirocin group,moxibustion 2 group,moxibustion 2+G1C1 group and 80,100 μg/mL G1C1 groups was significantly reduced on day 7 of treatment,and the quality of wound repair was better.Mupirocin,G1C1,moxibustion and moxibustion 2+G1C1 could effectively remove the residual bacteria on the wound surface,and the higher the mass concentration of G1C1,the lower the residual bacteria.Among them,the wound repair efficiency and bacterial residue of 80 μg/mL G1C1 group and moxibustion 2 group were very similar,and the wound repair efficiency of both was better than that of mupirocin group.In addition,it was also observed that the combination of materials and moxibustion had a better ability to clear wound bacteria than that used alone.(3)The results confirm that moxibustion,reduced graphene oxide/cerium dioxide nanocomposites and their combination have good anti-infection and wound healing effects.

Objective To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism.Methods Sixteen pregnant Kunming mice were randomly assigned into two groups(n=8)for intratracheal instillation of PBS or PM2.5 suspension at 1.5,7.5,and 12.5 days of gestation.The pregnancy outcome of the mice was observed,and placental zonal structure and vascular density of the labyrinth area were examined with HE staining,followed by detection of ferroptosis-related indexes in the placenta.In cultured human trophoblasts(HTR8/SVneo cells),the effects of PM2.5 exposure and treatment with metformin on cell viability,proliferation,migration,invasion,and tube formation ability were evaluated using CCK8 assay,EDU staining,wound healing assay,Transwell experiment,and tube formation experiment;the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting.Results M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight(all P<0.001).PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis.In cultured HTR8/SVneo cells,PM2.5 significantly inhibited proliferation,migration,invasion,and angiogenesis of the cells by causing ferroptosis.Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation,migration,invasion,and angiogenesis of the cells,and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity,reduced MDA and Fe2+ levels,and upregulated GPX4 and SLC7A11 protein expression(P<0.05 or 0.01).Conclusion PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice,and metformin can effectively alleviate PM2.5-induced trophoblast impairment.

This study aims to analyze the main drug resistance mechanism of Salmonella enteritidis induced by polymyxin in vitro.In this study,the resistance of Salmonella enteritidis CMCC(B)50335(ZK)to polymyxin was induced in vitro,and the growth characteristics,exercise ability,ul-trastructure and sensitivity to 16 antimicrobial agents before and after induction were determined by turbidimetry,semi-solid agar method,transmission electron microscope and disk diffusion method,and the whole genome and single nucleotide polymorphism(SNP)were detected by Illu-mina NovaSeq PE150 method.RT-qPCR was used to detect the differences in the expression levels of six drug-resistant related genes.The recombinant strain △phoPE1-128-1,which induced drug-resistant strain E1-128-1,was constructed by homologous recombination of Red Escherichia coli,and its sensitivity to polymyxin was detected.The results showed that three strains of induced drug-resistant bacteria E1-128-1,E1-128-3 and E2-128-3 were screened out,and the MIC increased by 128,64 and 64 times respectively after drug resistance stability test.Induced drug resistance had no significant effect on the growth ability of the tested bacteria and the sensitivity of 16 antibacte-rial drugs.The exercise ability of E1-128-1was significantly increased,and the cell wall and plasma membrane obviously thicken.There was no significant difference in the genome components of E1-128-1 before and after induction,but eight missense mutations of six drug-resistance related genes,including phoP/phoQ,cpxP,lptD,csrA and acrB,were detected,including four missense mutation sites of phoP,namely Leu185Trp,His189Ser,Thr190Tyr and Ile191His.The corresponding genes were sequenced by PCR,and the results were consistent with those of SNP.RT-qPCR results showed that the expression levels of mutant genes of the three induced strains increased signifi-cantly.Compared with E1-128-1,the MIC of △phoP E1-128-1 decreased to 1 mg/L.It is sug-gested that the mutation and increased expression of phoP gene are important factors for inducing polymyxin resistance of Salmonella CMCC(B)50335 in vitro.

Objective To investigate the influence of changes in blood flow parameters on pulse rate characteristics by taking the advantage of controllable parameters in an experimental cardiopulmonary bypass system.Methods A set of human circulatory system equipped with an in vitro wrist model was established.By changing parameters such as the heart rate,wrist flow,pressure,and system compliance,a photoplethysmography pulse wave signal was obtained from the wrist model,and the time-and frequency-domain indices of pulse rate variability were extracted.Results Changes in heart rate,pressure,and system compliance caused a change in pulse shape,but the time domain indices NN50 and PNN50,which indicate pulse rate variability,were zero,and the other indices and frequency domain indices were in the very low value category.Conclusions In the absence of heart rate variability,hemodynamic changes in heart rate,wrist flow,blood pressure,and system compliance did not produce significant pulse rate variability.This study can provide a reference for studies on pulse rate variability and heart rate using more convenient wrist acquisition equipment.

Objective To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism.Methods Sixteen pregnant Kunming mice were randomly assigned into two groups(n=8)for intratracheal instillation of PBS or PM2.5 suspension at 1.5,7.5,and 12.5 days of gestation.The pregnancy outcome of the mice was observed,and placental zonal structure and vascular density of the labyrinth area were examined with HE staining,followed by detection of ferroptosis-related indexes in the placenta.In cultured human trophoblasts(HTR8/SVneo cells),the effects of PM2.5 exposure and treatment with metformin on cell viability,proliferation,migration,invasion,and tube formation ability were evaluated using CCK8 assay,EDU staining,wound healing assay,Transwell experiment,and tube formation experiment;the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting.Results M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight(all P<0.001).PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis.In cultured HTR8/SVneo cells,PM2.5 significantly inhibited proliferation,migration,invasion,and angiogenesis of the cells by causing ferroptosis.Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation,migration,invasion,and angiogenesis of the cells,and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity,reduced MDA and Fe2+ levels,and upregulated GPX4 and SLC7A11 protein expression(P<0.05 or 0.01).Conclusion PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice,and metformin can effectively alleviate PM2.5-induced trophoblast impairment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.
Humans ; Acupuncture Therapy ; Periosteum ; Analgesia ; Pain Management ; Consciousness ; Pain

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1^Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.
Humans ; Male ; Fluorides/adverse effects* ; Semen ; Polymorphism, Genetic ; Glutathione Transferase/genetics* ; Glutathione S-Transferase pi/genetics* ; Infertility, Male/genetics* ; Genotype ; Biomarkers ; Genetic Predisposition to Disease ; Case-Control Studies