Postmenopausal osteoporosis (PMOP) is a chronic metabolic bone disease caused by a decrease in estrogen levels. With the acceleration of population aging process, the public health burden caused by it is becoming increasingly severe. The prevalence rate of osteoporosis in people over 65 years old in China is as high as 32%, which is especially prominent after menopause, which is about 5 times that of elderly men. About 40% of postmenopausal women are at risk of osteoporotic fractures, with a disability rate of up to 50% and a fatality rate of about 20%. The prevention and treatment of osteoporosis has become a major public health issue of global concern, and it is particularly urgent to develop reasonable and effective prevention and treatment programs and explore their scientific basis. Exercise is an important non-drug means for the prevention and treatment of PMOP, it can improve estrogen levels and the expression of bone formation transcription factors, and inhibit the levels of proinflammatory factors and bone resorption markers, macroscopically manifested by the improvement of bone microstructure and bone density. However, the effectiveness of exercise in improving bone mineral density (BMD) remains controversial. Some studies revealed significant changes of bone to mechanical stimulation, while others showed no significant effect of mechanical training, this heterogeneity in bone adapt to mechanical stimulation is particularly evident in postmenopausal women. Although the evidence that a wide range of exercise programs can improve osteoporosis, the optimal solution to address bone mineral loss remains unclear. The most effective exercise type, dosage and personalized adaptation are still being determined. This study will fully consider the differences in gender and hormone levels, searching and screening randomized controlled trials of PubMed, CNKI and other databases regarding exercise improving bone mineral density in women with PMOP. Strictly following the PRISMA guidelines to reviewed and compared the effects of different types of exercise modalities on BMD at different sites in women with PMOP by network Meta-analysis, to provide theoretical guidance to maintain or improve BMD in women with PMOP.

OBJECTIVE To explore the in vitro and in vivo inhibitory effects and mechanism of metformin on the malignant biological behavior of esophageal squamous cell carcinoma （ESCC） cells by the hypoxia inducible factor-1α （HIF-1α）/interleukin-8 （IL-8） signaling pathway. METHODS Human ESCC TE1 cells were assigned into blank group， metformin low-， medium-， and high-dose groups （0.5， 1， 2 mmol/L）， IDF-11774 （HIF-1α inhibitor） group （20 μmol/L）， and high-dose metformin+HIF-1α activator dimethyloxalylglycine （DMOG） group. After 24 h treatment， cell proliferation [measured by the positive rate of 5-ethynyl- 2′-deoxyuridine （EdU） and optical density at 450 nm （OD450 value）]， apoptosis， invasion and migration as well as mRNA expressions of proliferating cell nuclear antigen （PCNA）， Bcl-2 interacting mediator of cell death （Bim）， migration and invasion enhancer 1 （MIEN1）， and matrix metalloproteinase-9 （MMP-9）， and protein expressions of HIF-1α and IL-8 in the cells were detected. The xenograft tumor model of nude mice was established. Thirty nude mice were randomly divided into blank group， metformin low-， medium-， and high-dose groups （i.g. administration of metformin 62.5， 125， 250 mg/kg+i.p. administration of equal volume of normal saline）， IDF-11774 group （i.g. administration of 50 mg/kg IDF-11774+i.p. administration of equal volume of normal saline） and high-dose metformin+DMOG group （i.g. administration of metformin 250 mg/kg+i.p. administration of DMOG 250 mg/kg）， with 5 mice in each group. They were given relevant medicine， once a day， for 4 consecutive weeks； the mass and volume of the tumor and protein expressions of HIF-1α and IL-8 in the tumor tissue were determined. RESULTS The EdU positive rate， OD450 value， cell invasion number， scratch healing rate， mRNA expressions of PCNA， MIEN1 and MMP-9， protein expressions of HIF-1α and IL-8， as well as the mass and volume of transplanted tumors and protein expressions of HIF-1α and IL-8 in tumor tissues were decreased by metformin in concentration/dose-dependent manner （P＜0.05）. Additionally，metformin increased the apoptosis rate and mRNA expression of Bim in cells （P＜0.05）. The trend of changes in corresponding indicators in the IDF-11774 group was consistent with that in the metformin groups， whereas DMOG could significantly attenuate the aforementioned effects of high-concentration/high-dose metformin （P＜0.05）. CONCLUSIONS Metformin can inhibit the proliferation， invasion， migration of TE1 cells， and tumor growth of nude mice， and induce cell apoptosis， the mechanism of which may be related to the inhibition of HIF-1α/IL-8 signaling pathway.

Objective: To evaluate the bone repair effect of 3D-printed magnesium (Mg)-loaded polycaprolactone (PCL) scaffolds in a rat skull defect model. Methods: PCL scaffolds mixed with Mg microparticles were prepared by using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spectroscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague-Dawley (SD) rats, which were divided into the PCL group, PCL-Mg group, and untreated group, with 5 rats in each group. Micro-CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery. Results: The scaffolds had a pore size of (480 ± 25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL-Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL-Mg scaffolds was 68.97° ± 1.39°, indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL-Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating enhanced strength. The PCL-Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone volume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL-Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material. Conclusion PCL-Mg scaffolds can promote the repair of bone defects and have clinical potential as a new scaffold material for the repair of maxillofacial bone defects.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To explore the current situation of binary coping in patients with perimenopausal syndrome and analyze its influencing factors, in order to provide a basis for improving the level of binary coping.Methods:Using convenience sampling method, a total of 210 patients with perimenopausal syndrome and their spouses from the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine were cross-sectional surveyed by a general data questionnaire, the Binary Coping Scale, and the Modified Kupperman Score Scale. The influencing factors of binary coping level in patients with perimenopausal syndrome were explored by univariate analysis and variance decomposition model analysis.Results:A total of 200 valid questionnaires were retrieved.The patients aged (50.52 ± 2.89) years old. The binary coping score was (79.64 ± 22.74) points. The variance decomposition model analysis showed that marriage age, type of medical insurance, number of children, education level, family monthly income, spouse′s education level, presence of major comorbidities in spouse, modified Kupperman score, presence of generalized anxiety in spouse were the main influencing factors of binary coping in patients with perimenopausal syndrome (all P<0.05). Conclusions:The binary coping scores of patients with perimenopausal syndrome are lower than normal, and considering the influence and involvement of patients' spouses, nursing staff should pay special attention to patients who are married relatively early, have more children, have lower education levels, and have lower family monthly incomes. Additionally, attention should be given to spouses who experience widespread anxiety, have a lower level of education, and suffer from major chronic diseases. By developing and implementing comprehensive intervention measures aimed at improving the Kupperman score and the level of binary coping, both parties can be encouraged to support each other more effectively, thereby improving the marital relationships of patients during the perimenopausal period.

Objective To investigate the osteogenic properties of a methacrylated gelatin(GelMA)/bone marrow mesenchymal stem cells(BMSCs)composite hydrogel applied to the skull defect area of rats and to provide an experi-mental basis for the development of bone regeneration biomaterials.Methods This study was approved by the Animal Ethics Committee of Nanjing University.A novel photocurable composite biohydrogel was developed by constructing photoinitiators[lthium phenyl(2,4,6-trimethylbenzoyl)phosphinate,LAP],GelMA,and BMSCs.The surface morphology and elemental composition of the gel were examined using scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDX).The compressive strength of the gel was evaluated using an electronic universal testing ma-chine.After in vitro culture for 1,2,and 5 days,the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay,and their survival and morphology were examined through confocal microscopy.A 5 mm critical bone de-ficiency model was generated in a rat skull.The group receiving composite hydrogel treatment was referred to as the Gel-MA/BMSCs group,whereas the untreated group served as the control group.At the 4th and 8th weeks,micro-CT scans were taken to measure the bone defect area and new bone index,while at the 8th week,skull samples from the defect ar-ea were subjected to H&E staining,van Gieson staining,and Goldner staining to evaluate the quality of bone regenera-tion and new bone formation.Results SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology,the porosity of GelMA was 73.41％and the pore size of GelMA was(28.75±7.13)μm.EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel.The hydrogel compres-sion strength was 152 kPa.On the 5th day of GelMA/BMSCs culture,the cellular morphology transitioned from oval to spindle shaped under microscopic observation,accompanied by a significant increase in cell proliferation(159.4％,as determined by the CCK-8 assay).At 4 weeks after surgery,a 3D reconstructed micro-CT image revealed a minimal re-duction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group.At 8 weeks after surgery,no significant changes were observed in the control group's bone defect area,with only limited evi-dence of new bone growth;however,substantial healing of skull defects was evident in the GelMA/BMSCs group.Quan-titative analysis at both the 4-and 8-week examinations indicated significant improvements in the new bone volume(BV),new bone volume/total bone volume(BV/TV),bone surface(BS),and bone surface/total bone volume(BS/TV)in the GelMA/BMSCs group compared to those in the control group(P＜0.05).Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone,primarily consisting of fibrous connective tissue,at the defect edge in the control group.Conclusion Photocur-ing hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.