BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

BACKGROUND:The use of vancomycin in total knee arthroplasty is a controversial strategy for the prevention of incisional infection.At present,there is little evidence to evaluate the efficacy of this preventive measure in China. OBJECTIVE:To evaluate the efficacy of local vancomycin in the prevention of early postoperative incision infection during total knee arthroplasty. METHODS:120 patients with osteoarthritis of the knee who received unilateral total knee arthroplasty for the first time at Department of Joint Surgery of First Affiliated Hospital of Anhui Medical University from March to June 2022 were included in this study.They were randomly divided into the observation group and the control group,with 60 cases in each group.All patients gave informed consent to the treatment plan.In the observation group,1 g of vancomycin was applied intraoperatively;in the control group,no vancomycin was applied intraoperatively.Erythrocyte sedimentation rate,C-reactive protein,fever rate on seven consecutive days after surgery,degree of knee joint swelling,cumulative drainage volume,and incidence of periprosthetic joint infection were recorded in two groups of patients on days 1,3,and 5 after surgery so as to evaluate the efficacy of topical vancomycin in total knee arthroplasty for the prevention of incision infection in the early postoperative period. RESULTS AND CONCLUSION:(1)The differences in erythrocyte sedimentation rate and C-reactive protein between the two groups on days 1,3,and 5 after surgery were not significant(P>0.05).(2)The difference in fever rate between the two groups for 7 consecutive days after surgery was not significant(P>0.05).(3)There was no significant difference in the degree of postoperative knee swelling and cumulative drainage flow between the two groups(P>0.05).(4)The difference in the incidence of periprosthetic joint infection one year after surgery was not significant between the two groups(P>0.05).(5)The results suggest that the local use of vancomycin in total knee arthroplasty has not shown significant efficacy in preventing incision infection in the early postoperative period.

Objective:The emergence of polymyxin-resistant Klebsiella pneumoniae(KPN)in clinical settings necessitates an analysis of its antibiotic resistance characteristics,epidemiological features,and risk factors for its development.This study aims to provide insights for the prevention and control of polymyxin-resistant KPN infections. Methods:Thirty clinical isolates of polymyxin-resistant KPN were collected from the Third Xiangya Hospital of Central South University.Their antibiotic resistance profiles were analyzed.The presence of carbapenemase KPC,OXA-48,VIM,IMP,and NDM was detected using colloidal gold immunochromatography.Hypervirulent KPN was initially screened using the string test.Biofilm formation capacity was assessed using crystal violet staining.Combination drug susceptibility tests(polymyxin B with meropenem,tigecycline,cefoperazone/sulbactam)were conducted using the checkerboard method.Polymyxin-related resistance genes were detected by PCR.Multi-locus sequence typing(MLST)was performed for genotyping and phylogenetic tree construction.The study also involved collecting data from carbapenem-resistant(CR)-KPN polymyxin-resistant strains(23 strains,experimental group)and CR-KPN polymyxin-sensitive strains(57 strains,control group)to analyze potential risk factors for polymyxin-resistant KPN infection through univariate analysis and multivariate Logistic regression.The induction of resistance by continuous exposure to polymyxin B and colistin E was also tested. Results:Among the 30 polymyxin-resistant KPN isolates,28 were CR-KPN,all producing KPC enzyme.Four isolates were positive in the string test.Most isolates showed strong biofilm formation capabilities.Combination therapy showed additive or synergistic effects.All isolates carried the pmrA and phoP genes,while no mcr-1 or mcr-2 genes were detected.MLST results indicated that ST11 was the predominant type.The phylogenetic tree suggested that polymyxin-resistant KPN had not caused a hospital outbreak in the institution.The use of two or more different classes of antibiotics and the use of polymyxin were identified as independent risk factors for the development of polymyxin-resistant strains.Continuous use of polymyxin induced drug resistance. Conclusion:Polymyxin-resistant KPN is resistant to nearly all commonly used antibiotics,making polymyxin-based combination therapy a viable option.No plasmid-mediated polymyxin-resistant KPN has been isolated in the hospital.Polymyxin can induce resistance in KPN,highlighting the need for rational antibiotic use in clinical settings to delay the emergence of resistance.

Humans ; Inflammatory Bowel Diseases/drug therapy* ; Interleukin-6/therapeutic use*

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.

Objective:To clarify the evidences of hippocampal injury after radiotherapy avoiding hippocampus and explore its relationships with cognition.Methods:A prospective design was adopted in this study.A total of 183 patients with nasopharyngeal carcinoma treated by intensity modulated radiation therapy (IMRT group) and 30 matched healthy control (HC group)were collected in the Affiliated Hospital of Jiangsu University and Southeast University Affiliated Zhongda Hospital from January 2017 to December 2019. All subjects were assessed by Montreal Cognitive Assessment (MoCA-B) at baseline and 6 months after radiotherapy, then the patients with nasopharyngeal carcinoma were divided into cognitive impairment group and non-cognitive impairment group. Subjects were scanned with Siemens 3.0 T MR, and T 1WI was used as analysis sequence.The individual standardized hippocampus ROIs were extracted based on Montreal Neurological Institute(MNI) brain template.All texture features were calculated using the Radiomics developed by C++and Delphi, and the intra group correlation coefficients (ICC), average direction, machine learning (random forest) and autocorrelation matrix were used for reducing the features dimension. One-way ANOVA and generalized linear models were used to compare the differences among different groups. Pearson correlations analyses were used to evaluate the relationships between important texture features and clinical data. Logistic regressions were used to calculate the abilities of texture features to predict cognitive impairment. Results:After 9 patients who lost follow-up were excluded, a total of 164 patients with nasopharyngeal carcinoma were included as IMRT group.Texture features of ROIs were extracted and dimensionally reduced successfully. Five differences features (Variance, Entropy, GlevNonU, RLNonUni and Contrast)were found among HC group, cognitive impairment group and non-cognitive impairment group, and the last three further showed significant differences within IMRT group (GlevNonU, P=0.011;RLNonUni, P<0.001;Contrast, P<0.001). Hippocampal doses were positively correlated with Variance ( r=0.448, P<0.05), and negatively correlated with Entropy ( r=-0.461, P<0.05). There was a positive correlation between MoCA-B scores with GlevNonU, RLNonUniand Contrast ( r=0.503, P<0.05; r=0.587, P<0.05; r=0.531, P<0.05). GlevNonU and Contrast were independent predictors of cognitive impairment in hippocampal avoidance of radiotherapy (OR=0.731, 95%CI 0.610-0.857; OR=0.651, 95%CI 0.496-0.853). Conclusion:Results of texture analysis could be used as micro imaging evidences of hippocampal injury in radiotherapy avoiding hippocampus, and could also effectively predict the occurrences of cognitive impairment.

Objective:To investigate the safety and prognostic value of neoadjuvant chemotherapy and surgery for advanced gastric cancer patients with para-aortic lymph node metastasis.Methods:Clinicopathological data of 25 patients admitted to the Department of Gastrointestinal Surgery, Fujian Cancer Hospital from Jan 2015 to Jun 2017 were retrospectively analyzed. All patients were treated with SOX chemotherapy for 3 cycles. D 2 + paraaortic lymphadenectomy was performed in patients with stable disease (SD) . After operation, SOX regimen was used for 5 cycles of chemotherapy. Results:After 3 cycles of neoadjuvant chemotherapy, there were 2 cases with progressive disease, 6 cases of SD and 17 cases of partial remission. There was no treatment-related death. Twenty-three patients underwent surgery, including 19(76%) patients of R 0 resection. Tirty-four out of 128 para aortic lymph nodes were metastatic. Postoperative complications occurred in 5(22%) patients, with no mortality . The median progression free survival time and median overall survival time were 20 and 29 months respectively. The 1, 3-year overall survival rates were 80% and 48%, and the 1-year and 3-year progression free survival rates were 72% and 38%, respectively. For those with para-aortic lymph node metastasis the 1-year and 3-year OS rate were 70% and 17%, respectively. Multivariate analysis showed that the efficacy of neoadjuvant chemotherapy was an independent prognostic factor. Conclusion:Neoadjuvant chemotherapy is among others an independent prognostic factor affecting the post-op survival of advanced gastric carcinoma with para-aortic lymph node metastasis.

Objective To seperate fetal nucleated red blood cells (fNRBCs) from the whole maternal peripheral blood effectively by designing a circular channel microfluidic chip. Methods A microfluidic chip is designed by utilizing the margination in blood flow and the specific adhesion characteristics of immuno-agent anti-CD147. With the whole umbilical cord blood, the effects of different shear forces on the enrichment of fNRBCs was studied by immunofluorescence counting. Results Increasing shear rate in microfluidic chip could improve the number of captured fNRBCs compared with the static adhesion. With the increase of shear rate of blood flow, the number of the captured cells increased at first, and then decreased. Conclusions The use of microfluid chip can effectively seperate fNRBCs from the whole blood. The results provide an experimental reference for the non-invasive prenatal diagnosis research and the exploration on the mechanism of fetal cell migration.

Objective:To analyze the long-term efficacy and safety of thalidomide on refractory Crohn′s disease (CD).Methods:A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed.Results:In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95% CI 80.6%-96.6%), 80.7% (95% CI 70.3%-91.1%), 53.7% (95% CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio ( HR) of 3.559 for Crohn′s disease activity index (CDAI) ≥220(95% CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions:This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.

Objective To analyze the risk factor of delayed gastric emptying (DGE) and the impact of DGE on prognosis after radical gastrectomy of distal gastric carcinoma.Methods The clinical and pathological data of 1 447 distal gastric cancer patients undergoing gastrectomy from Jul 2007 to Jan 2018 at Fujian Tumour Hospital was analyzed retrospectively.Result DGE was found in 101 patients (7.0％),occurring at a median of (6.0 ± 2.1) d after surgery.It was significantly correlated with age,diabetes,hypoproteinemia,preoperative pyloric obstruction,operation time,surgical mode,anastomotic procedure,postoperative analgesia(all P ＜ 0.05).Multivariate analysis showed that hypoproteinemia,diabetes,pyloric obstruction in preoperative period,surgical mode,postoperative analgesia,anastomotic procedure were independently associated with DGE.The average hospitalization time for DGE was significantly higher than patients with non DGE(16.3 ± 4.2) d vs.(8.1 ± 2.1) d,P ＜ 0.05.The five-year survival of patients with DGE and non DGE were 54.9％ and 54.2％ respectively(P ＞0.05) Conclusion DGE prolonged hospital stay,but did not influence patients' prognosis.