The discovery in intestinal microflora changes during treatment of type 2 diabetes mellitus（T2DM）by dietary therapy，exercise therapy，traditional hypoglycemic drugs and bariatric surgery has arousedthe interest of medical world in the association between intestinal flora and T2DM. Meanwhile，the intestinal florahas also been proved to be closely related to the occurrence and development of T2DM. T2DM is treated by improv⁃ing its insulin resistance，in mechanism，mainly through regulating intestinal microflora，increasing the composi⁃tion of intestinal short ⁃chain fatty acid ⁃producing bacteria，reducing intestinal endotoxin and enhancing intestinalbarrier function by affecting bile acid metabolism and then reducing systemic inflammatory response. On this basis，the role of probiotics，prebiotics and fecal bacteria transplantation in the treatment of T2DM has been proposed andconfirmed. Although intestinal flora is considered as a new therapeutic target for T2DM in the future，the applica⁃tion of these new therapeutic approaches to intestinal flora has certain limitations in clinical application. The com⁃plexity of intestinal flora，evidence⁃based medicine of new therapeutic approaches and lack of clinical big data allrequire further exploration and research in the future.

Dysbiosis of intestinal flora in patients with sepsis results in the decrease of short⁃chain fattyacids（SCFA），metabolites of intestinal flora. Normal levels of SCFA can affect systemic immune homeostasis andenhance pathogen clearance. Therefore，regulating SCFA to restore immune homeostasis is an important treatmentfor patients with sepsis. In recent years，fecal bacteria transplantation and SCFA preparation have become newtherapies to regulate the level of SCFA in sepsis. This review focuses on the maintenance of intestinal immunity bySCFA through inhibition of histone deacetylase，G⁃protein⁃coupled receptor activation and aromatic hydrocarbonreceptor activation，and explores the research progress of SCFAin microbiome treatment of sepsis.

The airways and intestines of the human body are colonized with a large number of microorgan⁃isms. In recent years，studies have found that changes in the airways and intestinal flora affect the frequency andseverity of acute COPD attacks，and the metabolites of the intestinal flora is involved in the regulation of lunginflammation and immune response in patients with COPD，via the“gut⁃lung axis”. This article aims to review thecomposition and diversity of the lung and gut microbiome of COPD patients in different stages of the disease1course，as well as the effects of smoking and treatment methods on them，in order to provide a new direction forthe treatment of COPD.

Spinal cord injury is devastating damage to central nervous system. In addition to disabilityand death，it often results in a variety of complications which seriously affect life quality in patients. Meanwhile，intestinal flora is a complex and relatively stable ecosystem ，which is critical to maintaining human health. Inrecent years，the effects of intestinal flora on spinal cord injury have also received more and more attention.Studies have shown that intestinal flora can serve not only as a biomarker for the severity of spinal cord injury andpartial complications，but also as a good target for the treatment of spinal cord injury. Based on the results ofthese studies，this paper provides some ideas for the further research and clinical diagnosis and treatment of spinalcord injury.

Objective To explore the differences of intestinal flora between healthy Han and Tibetanpeople，so as to provide reference for race⁃microbiota hypothesis and the research on pathogenesis mechanism withmicrobiota as a study object. Methods A total of 128 fecal samples of healthy Han and Tibetan volunteers in thesame area were collected. 42 samples were screened by propensity score matching（PSM），including 14 Han and28 Tibetan samples. After high⁃throughput sequencing of the V3 plus V4 region in 16S rRNA gene of sample DNA，OTU table was generated and annotated. Based on the analysis of alpha and beta diversity，DESeq2 package andedgeR package of R language were used to analyze the difference in intestinal flora between Han and Tibetan；Net⁃work analysis was carried out by bnlean package，psych package and reshape2 package to screen the flora closelyrelated to ethnic factors，and the ethnic biomarkers of species at the genus level were identified by LEfSe analysis.Finally，the high⁃quality data were spliced and assembled by IDBA⁃UD software，the non⁃redundant gene set wasconstructed by CD⁃HIT software，and the metabolic pathway information and GO annotation results were obtainedby PICRUST analysis. The differences between the two groups were analyzed by STAMP software to compare thedifferences in metabolic pathways between the two groups. Results There were 199 different OTUs in intestinalflora between Han and Tibetan，proving that differences in intestinal flora existed between Han and Tibetan popula⁃tion. Ruminococcus，Anaeroplasma and Proteobacteria were significantly higher while Butyricum，Anaerostipes and Dialist were markedly lower in Tibetan intestinal flora than in Han flora. The flora closely related to ethnicfactors included Copri，Stercorea，and Haemophilus parainfluenzae. At the genus level，Pseudobutyricvibrio，Suc⁃cinicvibrio and Catenibaterium were the flora markers in Tibetan people，so were Dialster and Turibacter in Han.There were 10 different metabolic pathways. The significantly up⁃regulated pathways in the Tibetan group includedenzyme families，replication and repair，translation，nucleotide metabolism，metabolism of terpenoids andpolyketides. Conclusions This study partially verified the race⁃microbiota hypothesis. The influence of ethnic fac⁃tors should be considered in the study of flora and diseases.

Objective The quorum sensing system is related to bacterial growth profile，virulence，biofilmformation，motility，host immune responses，and resistance to antibiotics. The quorum sensing Escherichia coli（E. coli）regulator C（qseC）is the receptor of the E. coli quorum sensing system，and its effects on the physiologicaland biochemical characteristics of E. coli were not well understood. Methods In the present work，we used theThermotargetron gene targeting system（based on thermophilic mobile group Ⅱ intron）to inactivate the qseC genein E. coli strain HMS174. The phenotypic changes of ΔqseC627s strain，including growth rate，hemolysis，biofilmformation，motility，tolerance to the acidic and alkaline environment，and resistance to antibiotics，were investigated.The present work will draw a clearer picture of the physiological functions of the qseC gene in E. coli. Results The qseC627s locus of E. coli HMS174 was chosen as TeI3c/4c insertion site，the gene inactivation efficiency was100%. Targeting plasmid was cured by successively transferred in LB medium，and the plasmid cure efficiency was100%. Compared to the wild⁃type strain，the mutant ΔqseC627s showed reduced growth rate，maximum bacterialdensity，biofilm formation ability，motility，hemolytic ability，and tolerance to the acidic and alkaline. Further⁃more，compared to the wild type strain，the antibiotic susceptibility assay showed that ΔqseC627s was more resis⁃tant to chloramphenicol，ampicillin，tetracycline，amoxicillin，and metronidazole. Conclusions After the inacti⁃vation of the qseC gene in E. coli HMS174，the phenotype and resistance to external stress of the ΔqseC were sig⁃nificantly changed.

Objective To study the changes in body weight，blood lipids，blood sugar and LPS of miceon a high⁃fat diet under the intervention of calcium chloride，use 16S RNA high⁃throughput sequencing technologyto detect changes in the intestinal flora of high⁃fat mice，and explore the effect of calcium chloride on obesity in themice by regulation the composition of gut microbes. Methods Thirty male C57BL/6 wild⁃type mice were randomlydivided into control group（C），model group（M），and calcium chloride treatment group（D），10 in each group.Groups C，M and D were fed with standard feed plus drinking water，high⁃fat feed plus drinking water，and high⁃fat feed plus 1.5 g/100 mL calcium chloride for 11 weeks，followed by collecting the samples. The changes in bodyweight，blood lipids，blood sugar，LPS，and intestinal flora of different groups of mice were compared among thegroups. Results Calcium chloride significantly inhibited the weight gain of C57BL/6J mice on a high ⁃fat diet.After 11 weeks treatment with calcium chloride plus drinking water，the levels TC and blood sugar were significantlylowered，inflammatory factors IL⁃1β and IL⁃6 significantly decreased. IgM significantly increased，IgG significantlyincreased，and lipopolysaccharide significantly decreased in group D，as compared with group M. Calcium chlorideimproved the lipid disorders in the high⁃fat diet mice. Conclusion Calcium chloride can adjust the composition ofintestinal microbes so as to improve obesity in mice induced by high⁃fat diet.

Objective To observe the effect of Ginkgo biloba extract on nuclear factor erythroid relatedfactor 2（Nrf2）/heme oxygenase 1（HO⁃1）signaling pathway in the cochlea of presbycusis rats，and to explore themechanism of Ginkgo biloba extract in protection of presbycusis. Methods 45 SD rats were randomly divided in⁃to a control group，model group，Ginkgo biloba extract low⁃dose group，medium⁃dose group and high⁃dose group，9 for each group. Auditory function was detected by auditory brainstem response（ABR）. The serum contents ofmalondialdehyde（MDA）and total superoxide dismutase（T⁃SOD）were detected by ELISA. Ultrastructure of spiralganglion cells was observed under a transmission electron microscope. Changes in the structure and quantity of haircells in the Apical，Middle，or Basal turn were observed by immunofluorescence staining. Expression levels of Nrf2and HO⁃1 proteins in the cochlea were detected by immunohistochemistry and Western blotting. Results As com⁃pared with those in the control group，the ABR threshold in the model group was significantly increased，the serumcontent of MDA was increased，whereas that of T ⁃SOD was decreased；the ultrastructure of spiral ganglion cellswas obviously destroyed，the morphology of the inner and outer hair cells were disordered，the number of hair cellswas greatly reduced，and the expression levels of Nrf2 and HO ⁃1 proteins were down ⁃ regulated. After treatmentwith different doses of Ginkgo biloba extract，as compared with those in the model group，the ABR threshold wassignificantly reduced，the content of MDA was reduced，the content of T⁃SOD was increased，the ultrastructure ofspiral ganglia cells was significantly improved，the morphology of inner and outer hair cells were clear and the cellnumber gradually increased，and the expression levels of Nrf2 and HO ⁃1 proteins were up ⁃ regulated. Conclusions Ginkgo biloba extract can alleviate oxidative stress damage in the cochlea of presbycusis rats，and its mechanismmay be related to the regulation of Nrf2/HO⁃1 signaling pathway.

Objective To investigate the effect and molecular mechanism of cMyc inhibitor 10058⁃F4 onleukemia THP1 cells. Methods Human leukemic THP1 cells were cultured in vitro and treated with differentconcentrations（1，5，10，50，100 μmol/L）of cMyc inhibitor 10058⁃F4. The effect of cell growth inhibition wasmeasured by CCK ⁃8 assays. The changes of apoptosis and mitochondrial membrane potential were measured by Calcein/PI and JC ⁃1 fluorescence staining，respectively. The cell cycle was determined by flow cytometry. Theexpression levels of apoptosis ⁃ related proteins（Cleaved ⁃Caspase ⁃3 and Bax）and DNA damage response ⁃ relatedproteins（pATM and γH2AX）were analyzed by Western blot. Results Different concentrations of 10058⁃F4significantly inhibited THP1 cell proliferation in concentration⁃dependent and time⁃dependent manners. 10058⁃F4induced apoptosis and reduced mitochondrial membrane potential levels in a concentration⁃dependent way，and thedifference was statistically significant（P < 0.05）. Cell cycle assays showed that 10058⁃F4 could induce phase G2/M arrests in THP1 cells. Western blot experiments showed that the expression of the apoptotic（Cleaved⁃Caspase⁃3and Bax）and DNA damage related proteins（pATM and γH2AX）were significantly increased in THP1 cells treat⁃ed with 10058⁃F4，and the difference was statistically significant（P < 0.05）. Conclusions The cMyc inhibitor10058⁃F4 could induce the apoptosis of leukemic THP1 cells by inducing cellular DNA damage and activating rele⁃vant signal pathways.

Objective To explore the firing activity of the ventromedial thalamic nucleus（VM）in ratswith unilateral 6⁃OHDA lesions. Methods The recording electrodes were implanted in the bilateral ventromedialthalamic nucleus of SD rats via stereotactic surgery，and the stainless steel cannula for 6⁃OHDA injection was im⁃planted above the right medial forebrain bundle. The unilateral Parkinson′s disease rat model was induced by injec⁃tion of 12 μg/4 μL 6⁃OHDA into the right medial forebrain bundle. Extracellular signals in the bilateral VM wererecorded in vivo using multi ⁃channel methods before and after lesion. Tyrosine hydroxylase immunohistochemicalstaining was used to detect the damage of dopaminergic neurons in substantianigra. Cresol violet staining was usedto determine the positions of the tips of the recording electrodes. Results In model rats，the mean firing rates ofneurons in the left VM and the right VM were（15.528 7 ± 0.572 69）Hz and（5.698 1 ± 0.279 1）Hz，respectively，with significant difference（t = 15.431，P < 0.001）. Compared with that before the establishment of the model，themean firing rates of neurons in the right VM decreased significantly after the establishment of the model（F =306.701，P < 0.001）. Before and after the model′s establishment，the rates of burst firing neurons in the right VMwere 14.8 % and 44.4 %，respectively. Compared with that before the establishment of the model，the proportionof burst firing neurons in the right VM was significantly higher after the establishment of the model（P = 0.001）.Compared with that in the left VM，the proportion of burst firing neurons in the right VM increased significantly in the model rats and the difference was statistically significant（χ2 = 8.355，P = 0.004）. Conclusion In rats withunilateral 6⁃OHDA lesions，the firing activity of the ventromedial thalamic nucleus changed significantly. The ven⁃tromedial thalamic nucleus may be important in the pathophysiology of Parkinson′s disease.

Objective To observe the ameliorating effect of EGCG on respiratory failure induced by hypoxiain rats with cor pulmonale. Methods Fifty rats were randomly divided into normal control group（normal oxygen+normal saline），model group（hypoxia+normal saline），low⁃dose EGCG group（hypoxia+10 mg/kg EGCG），high⁃dose EGCG group（hypoxia+50 mg/kg EGCG）and positive control group（hypoxia+1.0 mg/kg naloxone hydrochlo⁃ride），with 10 rats in each group. After 4 weeks of intervention，the lung function⁃related indexes，arterial bloodgas related indexes，serum interleukin⁃8（IL⁃8），and tumor necrosis factor⁃α（TNF⁃α）were detected. Hemody⁃namics and right heart index were detected. Results Compared with those in the normal control group，breathrate，peak expiratory flow rate（PEF），and 50% vital capacity maximum expiratory flow（FEF50），hydrogen ionconcentration（pH），oxygen partial pressure（PaO2），decreased，expiratory resistance，carbon dioxide partialpressure（PaCO2），serum interleukin⁃8（IL⁃8），tumor necrosis factor⁃α（TNF⁃α），average Pulmonary artery pres⁃sure（mPAP），and right heart index increased in model group，low⁃dose EGCG group，high⁃dose EGCG and posi⁃tive control group（P < 0.05）. Compared with those in the model group，breath rate，PEF，FEF50，pH，and PaO2level increased；but expiratory resistance，PaCO2，IL⁃8，TNF⁃ α，mPAP，and right heart index decreased inlow⁃dose EGCG group，high⁃dose EGCG and positive control group（P < 0.05）. Compared with those in the low⁃doseEGCG group，breath rate，PEF，FEF50，pH，and PaO2 level increased，while expiratory resistance，PaCO2，IL⁃8，TNF ⁃ α，mPAP，and right heart index decreased in high ⁃dose EGCG and positive control group（P < 0.05）.Conclusion EGCG can enhance pulmonary ventilation function induced by hypoxia in rats with cor pulmonale，which can diminish the inflammation response，reduce the right heart load，thus has good improvement effect onaspiration failure.

Objective To study the similarities and differences in iron supplementation effect betweenpregnant women with beta thalassemia minor combined with iron deficiency anemia（IDA）and those with simpleIDA，and explore monitoring methods for iron supplementation. Methods A total of 214 pregnant women visitingfor regular pregnancy check⁃ups were enrolled in the study，including 52 cases of beta thalassemia minor combinedwith IDA，53 cases of simple beta thalassemia minor，50 cases of simple IDA，and 59 cases of healthy pregnantwomen. Those in the beta thalassemia minor combined with IDA group and the simple IDA group were managedwith oral iron supplementation for 4 weeks. The blood parameters and iron metabolism parameters of each pregnantwoman were examined and compared across the groups. Results （1）The sTfR content in the beta thalassemiaminor combined with IDA group was significantly higher than that in the simple beta thalassemia minor and thesimple IDA groups（P < 0.05）.（2）After iron supplementation，the levels of Hb，MCV and all iron metabolismparameters were significantly improved in the groups of the beta thalassemia minor combined with IDA and the simpleIDA（P < 0.05）.（3）After iron supplementation，the increase of ferritin in the beta thalassemia minor combinedwith IDA group was significantly greater than that in the simple IDA group（P < 0.05）. Conclusion Iron supple⁃mentation for pregnant women with mild thalassemia is effective，with a lower risk of iron overload. The ferritin andsTfR detections are helpful for accurate understanding of the iron status and timely screening of iron deficiency inthose pregnant women. It is meaningful for the clinical guidance for iron supplementation.

Objective To investigate the risk factors and outcomes of delayed platelet engraftment（DPE）after unrelated umbilical cord blood transplantation（UCBT）. Methods The clinical data of 318 patients withmalignant hematological diseases treated by UCBT were retrospectively analyzed. According to the time of plateletengraftment，they were divided into the delayed platelet engraftment（DPE）group and the normal（non ⁃ DPE）group for further analysis Univariate and multivariate analysis were used to analyze risk factors of DPE. Coxre⁃gression analysis was used to analyze the effect of DPE on prognosis. Results The incidence of DPE afterUCBT in all patients was 22.01%. The median time of platelet engraftment for the non ⁃DPE and DPE groupswere 93（69，123）days and 32（13，60）days. Allele ⁃level HLA mismatch（< 6/8），lower infused CD34 + cellcount（≤ 1.7 × 105/kg），CMV viremia and grade Ⅱ⁃ⅣaGVHD preplatelet engraftment were high risk factors forDPE after UCBT. The probability of overall survival（OS）and disease free survival（DFS）at 3 years were 32.9%and 74.0%（P < 0.001），32.9% vs. 68.1%（P < 0.001）in the DPE and non⁃DPE group. DPE，weight ≥ 48 kg，and Ⅲ~Ⅳ a GVHD are risk factors that affecting survival rate. Conclusion DPE after UCBT was associated withworse OS. Early identification of risk factors could be beneficial for the managements of complications.

Objective To analyze the short⁃term and long⁃term effects of tricuspid annuloplasty with autol⁃ogous pericardial soft ring on left ventricular dysfunction. Methods Eighty patients with tricuspid regurgitationcomplicated with left ventricular dysfunction treated in our hospital from January 2014 to January 2015 were ran⁃domly divided into control group and observation group. The former was treated with de Vega tricuspid valvuloplastyand the latter with autologous pericardial soft ring tricuspid valvuloplasty. The general data of the two groups werecollected and compared. The changes of cardiac function in both groups were examined. The two groups were com⁃pared in terms of the number of patients with moderate or above tricuspid regurgitation，5⁃year readmission rate，5 ⁃ year survival rate and postoperative complications. Results The levels of RVD and LAD in the observationgroup were significantly lower than those in the control group，and the levels of LVED，Co，LVEDd and LVEF inthe observation group were significantly higher than those in the control group（P < 0.05）. The level of TRAs in thepatients with severe reflux in the observation group was significantly lower than that in those with severe reflux inthe control group（P < 0.05）. In 5 years after operation，the number of patients with moderate tricuspid regurgitationand 5⁃year readmission rate in the observation group were significantly lower than those in the control group，andthe 5⁃year survival rate was significantly higher than that in the control group（P < 0.05）. Conclusion Autologouspericardial soft ring tricuspid annuloplasty is simple，safe and effective in the treatment of tricuspid regurgitationcombined with left ventricular insufficiency，and it can quickly restore the cardiac function of patients in the earlystage，and its effect during the follow⁃up period is significantly better than De Vega tricuspid annuloplasty. It cansignificantly improve their quality of life and prolong their life.

Objective To explore the effect of Colaizzi analysis combined with cognitive⁃behavior therapy（CBT）for adolescent non⁃suicidal self⁃injury（NSSI）. Methods A total of 126 young NSSI patients treated in ourhospital were randomly assigned to two groups with 63 cases in each group. Patients in the control group receivedColaizzi analysis alone，and patients in the observation group received Colaizzi analysis combined with CBT inter⁃vention. Self⁃injury behavior，explicit aggressive behavior，life stress events，health⁃related risk behaviors，familyintimacy and adaptability in each group were evaluated and compared. Results After the intervention，the scoresof functional assessment of self⁃mutilation（FASM）behavior questionnaire，moas speech，property，self and physi⁃cal aggression，Barratt impulsiveness scale（BIS），adolescent self⁃rating life events check list（ASLEC）and ado⁃lescent health related risk behavior inventory（AHRBI）decreased significantly. The scores of FACES II⁃CV（familyadaptability and cohesion scale II ⁃CV）functional questionnaire increased significantly，and the change range ofthe observation group was higher than that of the control group（P < 0.05）. Conclusion Colaizzi analysis combinedwith CBT therapy could significantly reduce the incidence of NSSI and life stress events，improve their aggressionand impulsivity，and improve family intimacy. This psychological intervention has important application value andis worthy of clinical promotion and application.

Objective To compare the efficacy and safety of sugammadex versus neostigmine for reversal ofresidual neuromuscular blockade in patients undergoing simultaneous pancreas ⁃ kidney transplantation. Methods The patients undergoing simultaneous pancreas⁃kidney transplantation from January 2017 to May 2021 were includedand divided into 2 groups：sugammadex group（group S）and neostigmine group（group N）. Demographic charac⁃teristics，effective time，spontaneous breathing recovery time，extubation time，post⁃anesthesia care unit（PACU）stay and hospital stay were recorded. The two groups were compared in terms of postoperative complications，creati⁃nine clearance rate，serum amylase and fasting blood glucose before surgery and on the 1st，3rd，7th，14th daypostoperatively. Results A total of 152 patients were enrolled：82 in group S and 70 in group N. Compared withgroup N，the effective time，spontaneous breathing recovery，extubation time and PACU stay in group S weremuch shorter. The incidences of postoperative hypoxemia and pulmonary infection of group S were much lower thangroup N（P < 0.05）. There were no statistically significant differences in the creatinine clearance rate and thelevels of serum amylase and fasting blood glucose as well as in the incidences of other postoperative complicationsbetween the two groups. Conclusions Sugammadex is better than neostigmine at promoting the reversal of residualneuromuscular blockade and lowering postoperative pulmonary complications.

Objective To analyze the clinical value of 3D printing combined with subtalar arthroscopy intreatment of calcaneal fractures. Methods 128 patients with Sanders Ⅱ⁃Ⅳ calcaneal fractures diagnosis in thehospital from January 2019 to August 2020 were chose and randomly divided into the control group and the observa⁃tion group，where 64 patients were respectively included. The control group was treated with subtalar arthroscopicpercutaneous open reduction and internal fixation. The observation group was treated with 3D printed calcanealfracture model and simulated surgery scheme before operation. The two groups were followed up until August 2021，with follow⁃up time of 12~31 months and median time of 25 months. The operation related indexes including time，bleeding volume and complications，postoperative stay⁃in hospital days and fracture healing time，joint functionincluding Böhler angle，Gissane angle and American Orthopaedic Foot and ankle Association（AOFAS）score werecompared between the two groups. Results There were no differences of operative time and bleeding volumebetween the two groups（P > 0.05），while the incidence of complications in observation group was lower than thatin control group（P < 0.05）. The stay⁃in hospital days and fracture healing time in the observation group were shorterthan those in the control group（P < 0.05）. Böhler angle and gissane angle in the two groups increased after treat⁃ment. But those in observation group were significantly higher than control group（P < 0.05）. The excellent andgood rate of foot and ankle function inobservation group was higher than control group（P < 0.05）. Conclusion Preoperative 3D printing combined with subtalar arthroscopic minimally invasive treatment of Sanders Ⅱ-Ⅳ calca⁃neal fractures has good clinical safety and efficacy. It can greatly reduce perioperative complications and shortenfracture healing and rehabilitation time，while improving foot and ankle function.

Skull defects is a common and important clinical condition in neurosurgery. Using the osteogenicproperties of stem cells to repair bone defects of critical size has become the focus of attention. Application ofvarious stem cells has presently made significant progress in bone tissue engineering. However，how to improve theimplantation rate and survival rate of stem cells is the key to this repair method. Therapies with stem cells for skulldefects have been proven feasible in animal studies，providing a new way for further clinical research. Stem celltransplantation is still the most promising procedure for repairing skull defects.