Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to eluci-date its underlying mechanisms in the context of Crohn's disease(CD)development.Mouse colitis models were established by dextran sulfate sodium(DSS)treatment.Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry,respectively.Antibiotic-treated mice served as models for microbiota depletion and transplantation.The expression of forkhead box P3+(FOXP3+)regulatory T cells(Tregs)was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort.THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile,with an increased abundance of probiotics Bacteroides fragilis,while pathogenic bacteria were depleted.In addition,THA increased beneficial metabolites bile acids and significantly restored gut barrier function.Transcriptomic profiling revealed that THA inhibited interleukin-17(IL-17),IL-1β and cell cycle signaling.Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA.Specifically,increased level of gut commensal B.fragilis was observed,correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid(7-ketolithocholic acid,7-KA)following THA treatment.This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1(FXR1)to inhibit auto-phagy.An interaction between FOXP3 and FXR1 was identified,with binding regions localized to the FOXP3 domain(aa238-335)and the FXR1 domain(aa82-222),respectively.Conclusively,THA modu-lates the gut microbiota and metabolite profiles towards a more beneficial composition,enhances gut barrier function,promotes the differentiation of FOXP3+Tregs and curbs pro-inflammatory pathways.

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To investigate the gut microbial characteristics in patients with acute ischemic stroke and resilience of the gut microbiota after a stroke. Methods Ninety-five fecal samples from 28 ischemic stroke patients and 28 fecal samples from 28 healthy volunteers were collected.DNA was extracted from these samples and the bacterial 16S rRNA were amplified through real-time quantitative polymerase chain reaction (qPCR). All PCR products were mixed together and then sequenced using the Illumina Hiseq 2500 platform. Microbiome analysis was implemented in QIIME. Results Patients with acute ischemic stroke showed significantly higher diversity than controls (phylogenetic diversity, P=0.002). The overall composition of the gut microbial communities also differed significantly between acute ischemic stroke patients and healthy controls as indicated by the clear separation in principle coordinate analysis (Adonis test on Bray-Curtis, P<0.001). Stroke patients' intestines had more opportunistic pathogens, such as Enterobacteriaceae, Veillonellaceae and Streptococcaceae, fewer commensal or beneficial genera including Bacteroides and Prevotella. Four weeks after onset, the gut microbiota in stroke patients began to restore, but the alpha diversity declined (P<0.05). Conclusion The present study has revealed the characteristic of gut microbial dysbiosis and recovery in acute ischemic stroke patients.However,the significance of the dynamic gut microbiota in stroke patients needs further study.

OBJECTIVETo investigate the features and causes of complications of unilateral pedicle screw fixation combined with contralateral percutaneous translaminar facet screw fixation and lumbar interbody fusion in treating lower lumbar diseases.

METHODSThe clinical data of 166 patients with lower lumbar diseases who underwent unilateral pedicle screw fixation combined with contralateral percutaneous translaminar facet screw fixation and lumbar interbody fusion with intervertebral cages from January 2008 to December 2013 were retrospectively analyzed. There were 64 males and 102 females, aged from 24 to 74 years with a mean of 51.9 years old, suffered from lower lumbar lesions for 47.5 months on average (ranged, 8 months to 30 years). Among these patients, lumbar intervertebral disc degeneration was found in 49 patients, recurred lumbar intervertebral disc protrusion in 17 patients, massive lumbar intervertebral disc protrusion in 23 patients, lumbar intervertebral disc protrusion accompany with spinal canal stenosis in 27 patients, lumbar degenerative spondylolisthesis with degree I (Meyerding grade) in 21 patients, far lateral lumbar intervertebral disc protrusion in 5 patients. Single segmental diseases occurred in 124 patients and two segmental diseases in 42 patients. The diseases occurred at L(3,4) segment in 6 patients, at L(4,5) segment in 97 patients, at L5S1 segment in 21 patients, at L(2,3), and L(3,4) segments in 1 patient, at L(3,4) and L4,5) segments in 26 patients, and at L(4,5), and L5S1 segments in 15 patients.

RESULTSThere was no abnormal bleeding in the patients and no patient received blood transfusion. During the surgery, spinal dura mater injury with cerebrospinal fluid leakage complicated in 1 patient, a fracture of vertebral pedicle in 4 patients, and end plate injury in 2 patients. No postoperative cerebrospinal fluid, incision infection and skin necrosis were found after operation. Nerve root injury was found in 1 patient. According to the position of pedicles crew, 371 screws of 163 patients were in degree I and 3 screws of 3 patients were in degree II; position of translaminar facet screw, 199 screws of 157 patients were type I, 8 screws of 8 patients were type II, 1 screw of 1 patient was III. Translaminar facet screw was slightly short in 2 patients. Five patients were lost to follow-up, two patients were died. The remaining patients were followed up for 35.4 months on average (ranged, 12 to 60 months). During the follow-up period , end plate was cut off and intervertebral cages were embedded in 14 segments of 14 patients. Abnormal pain of both lower extremities was found in 1 patient. With the exception of 11 unidentified segments in 11 patients, 189 segments of 148 patients obtained intervertebral fusion. No loosening, displacement, breakage of pedicle screw or translaminar facet screw, displacement of intervertebral cages or obvious degeneration of adjacent segments were found. The coronal and sagittal planes balance of lumbar vertebra were obviously improved. Postoperative JOA score was significantly increased than that of preoperative.

CONCLUSIONUnilateral pedicle screw fixation combined with contralateral percutaneous translaminar facet screw fixation and lumbar interbody fusion with intervertebral cages is a good choice for the treatment of lower lumbar diseases, but it has a risk of complications. Abundant surgeon's surgical experience, careful operation, and rational use of imaging technique can effectively reduce the incidence of complications.

Adult ; Aged ; Bone Plates ; Female ; Humans ; Internal Fixators ; Intervertebral Disc Degeneration ; surgery ; Intervertebral Disc Displacement ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Retrospective Studies ; Spinal Fusion ; Spondylolisthesis ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the advantages and disadvantages of unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion with cages in the treatment of two-level lumbar vertebra diseases, by comparing bilateral pedicle screw fixation and interbody fusion with cages.

METHODSForty-nine patients with two-level lumbar diseases who received treatments from June 2009 to December 2011 were included in this study. Among these patients, 23 patients received unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion with cages (combined fixation group) and the remaining 26 patients underwent bilateral pedicle screw fixation and interbody fusion with cages (bilateral fixation group). These patients consisted of 17 males and 32 females, ranging in age from 29 to 68 years old. Among these patients, lumbar intervertebral disc herniation accompanied by the spinal canal stenosis was found in 29 patients, degenerative lumbar disc diseases in 17 patients and lumbar degenerative spondylolisthesis (degree I) in 3 patients. The lesions occurred at L2,3 and L3,4 segments in 1 patient, at L3,4 and L4,5 segments in 30 patients, and at L4,5 segment and L5S1 segment in 18 patients. Wound length, operation time, intraoperative blood loss and postoperative wound drainage were compared between two groups. Intervertebral space height in the lesioned segment before and during surgery and at the latest follow up was also compared between two groups. Before surgery and at the latest follow-up, the Cobb angle of the coronal plane and sagittal plane of the lumbar spine, loosening or breakage of internal fixations, the dislocation of intervertebral cages, and interbody fusion were all evaluated in each group. The visual analogue scale (VAS) was used to measure lumbar incision pain. The Japanese Orthopedic Association (JOA) scoring system was used to evaluate the function before surgery and at the latest follow-up.

RESULTSNo wound infection or skin necrosis was observed after surgery in all patients. No cerebrospinal fluid leakage, nerve root injury, cauda equia injury or worsened neural function in the lower limb occurred in all patients during and after surgery. Wound length, operation time, intraoperative blood loss and postoperative wound drainage in the combined fixation group were superior to those in the bilateral fixation group. At postoperative 72 hours, the VAS score in the combined fixation group (1 to 4 points, mean 2.35±1.20) was significantly lower than that in the bilateral fixation group (2 to 5 points, mean 3.11±1.00; P<0.05). All the patients were followed up for 12 to 48 months, with a mean of 29 months. After surgery, intervertebral space height was well recovered in each patient and it was well maintained at the latest follow-up, and there was no significant difference between two groups (P>0.05). During follow-up, pedicle screw and translaminar facet screw loosening, dislocation or breakage and dislocation of intervertebral cages were all not found. At the latest follow-up, the Cobb angle of the coronal plane and sagittal plane of the lumbar spine was obviously improved and was not significantly different between two groups (P>0.05). The lumbar interbody fusion rate was 93.5% and 96.2% in the combined fixation group and bilateral fixation group, respectively, and there was no significant difference between them (P>0.05). There was a significant difference in JOA score between before surgery and at the latest follow-up in each patient (P<0.05), and at the latest follow-up, significant difference in JOA score was found between two groups (P<0.05).

CONCLUSIONCompared to bilateral pedicle screw fixation and lumbar interbody fusion with cages, unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and lumbar interbody fusion with cages shows advantages including small skin incision, minimal invasion, ease of operation, highly reliable stability, high interbody fusion rate, rapid recovery in the treatment of two-level lumbar vertebra diseases and therefore can be preferred as a treatment method of this disease.

Adult ; Aged ; Female ; Humans ; Intervertebral Disc Degeneration ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Spinal Fusion ; methods ; Spinal Stenosis ; surgery ; Spondylolisthesis ; surgery

OBJECTIVETo compare the advantages and disadvantages of unilateral pedicle screw fixation plus lumbar interbody fusion and unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation plus lumbar interbody fusion in treating single segmental lower lumbar vertebra diseases.

METHODSSixty-two patients with single segmental lower lumbar vertebra disease who received treatment between January 2008 and June 2009. These patients were consisted of 16 males and 46 females, ranging in age from 27 to 72 years old, with a mean age of 51.6 years old. Among these patients, lumbar degenerative disease had in 22 patients, recurrence of lumbar intervertebral disc protrusion in 13 patients, lumbar intervertebral disc protrusion accompany with spinal canal stenosis in 12 patients, massive lumbar intervertebral disc protrusion in 5 patients and lumbar degenerative spondylolisthesis with degree I in 10 patients. The lesions occurred at L3,4 segment in 5 patients, at L4,5 segment in 42 patients, and at L5S1 segment in 15 patients. Thirty patients underwent unilateral pedicle screw fixation (unilateral screw fixation group, group A) and thirty-two patients received unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation (bilateral screw fixation group, group B). Lumbar interbody fusion with intervertebral cages was also performed in all patients. Incision length, operation time, intraoperative blood loss and postoperative wound drainage were compared between two groups. Loosening or breakage of internal fixations, displacement of intervertebral cages and interbody fusion conditions were observed in each group. Preoperative and postoperative intervertebral height, coronal and sagittal Cobb angle and wound pain at 72 h after operation were compared between two groups. The Japanese Orthopedic Association (JOA) scoring system was used to evaluate the cinical effects.

RESULTSNeither wound infection, skin necrosis, nerve root or cauda equia injury, nor worsened neurological dysfunction in the lower limb occurred in each group. There were no significant differences in incision length, intraoperative blood loss and postoperative wound drainage between two groups. The operation time in group A was significantly shorter than that of group B (P < 0.05). There were no significant differences in visual analogue scale value of the wound pain at postoperative 72 h between two groups (P > 0.05). All patients were followed up for 12-48 months,with a mean of 27.5 months. The intervertebral height of all patients had obviously recovered at 5 days after operation, furthermore, at the final follow-up, it still had well maintained. During follow-up, no pedicle screw and/or translaminar facet screw loosening, displacement or breakage and displacement of intervertebral cages were found. The lumbar interbody fusion rate was 96.7% and 96.9% in group A and group B, respectively, and there was no significant difference between two groups (P > 0.05). JOA score of all patients got obviously improved after operation (P < 0.05) and there was no significant difference between two groups (P > 0.05).

CONCLUSIONBoth unilateral pedicle screw fixation plus lumbar interbody fusion and unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation plus lumbar interbody fusion have advantages of small incision, minimal invasion, simple operation, reliable stability, high interbody fusion rate,rapid recovery, encouraging clinical effects and less complications. Compared with unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation, the operation of unilateral pedicle screw fixation is simpler and can avoid using special equipments. Therefore, unilateral pedicle screw fixation plus lumbar interbody fusion can be used in treating single-segmental lower lumbar vertebra diseases under the precondition of strictly grasping indications for surgery and improving surgical skills.

Adult ; Aged ; Bone Screws ; Female ; Humans ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Spinal Diseases ; surgery ; Spinal Fusion ; methods

OBJECTIVETo investigate the feasibility of utilizing self-designed score system for lower lumbar vertebral burst fractures to select surgical approach.

METHODSFrom January 2006 to December 2011, the clinical data of 56 patients with lower lumbar vertebra burst fractures who underwent surgical treatment were retrospectively analyzed. There were 42 males and 14 females with an average age of 43.1 years old (ranged, 19 to 65). Causes of injury included falling down (40 cases), traffic accidents (12 cases), and crashing injury by heavy objects(4 cases). Injury site was L3 in 37 cases, L4 in 16 cases, and L5 in 3 cases. According to the AO classification, 17 cases were type A3.1, 14 cases were type A3.2, 25 cases were type A3.3. According to Frankel grade of nerous function, 2 cases were grade B, 5 cases were grade C, 9 cases were grade D and 40 cases were grade E. Surgical methods and approaches were chosen based on the comprehensive evaluation of AO classification, condition of posterior column injury and spinal canal encroachment. Surgical methods and approaches included trans-vertebra fixation (15 cases), intra-vertebra pedicle screw fixation (21 cases), combination of anterior and posterior approaches (11 cases), one-stage posterior approaches (9 cases). Cobb angles, restorations of the affected vertebral anterior border height, and conditions of spinal canal encroachment were compared before and after surgery. Conditions of bone graft fusion and internal fixation (if bending, loosening or breakage existed) were observed. Spinal cord functions were assessed according to Frankel grade. Localized pain and working status of patients were also assessed at the last follow-up.

RESULTSNo incision infection was found and no spinal nerve symptoms improved in all of 56 patients. All patients were followed up for 12 to 60 months with a mean of 28.5 months, without internal fixation loosening or breakage. There was significant differences in Cobb angle, vertebral anterior border height and recovery of spinal canal encroachment between preoperative and postoperative instantly (P < 0.05), however, there was no significant difference between postoperative instantly and final follow-up (P > 0.05). Thirteen cases obtained fusion by trans-vertebra fixation, 20 cases obtained fusion by intra-vertebra fixation, and 20 cases were treated by the combination of anterior and posterior approaches or one-stage posterior approaches all of patients obtained fusion. Spinal nervous function recovered I to II grade, 1 case was grade C, 3 cases were grade D, 52 cases were grade E. Localized pain was assessed as P1 in 52 cases, P2 in 3 cases, and P3 in 1 case. Working status was classified into W1 in 12 cases, W2 in 39 cases, and W3 in 5 cases.

CONCLUSIONThe lower lumbar vertebra and thoracolumbar junction exhibit different injury characteristics due to variations in anatomy and biomechanics. A comprehensive score of the AO classification, posterior column injury and degree of spinal canal encroachment will guide the selection of surgical method and approach for the treatment of lower lumbar vertebra burst fractures.

Adult ; Aged ; Biomechanical Phenomena ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; methods ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Spinal Fractures ; surgery ; Spinal Fusion ; methods

Objective To investigate the effects of Shenfu injection on blood pressure and heart rate of patients receiving carotid artery stenting.Methods One hundred and twenty patients were randomly divided into the treatment group and the control group , sixty cases in each group.The control group received conventional medication under custodial care , and the treatment group was given Shenfu ( 1 mL · kg -1 ) 10 minutes before surgery.Mean arterial pressure(MAP), heart rate (HR), oxygen satu-ration (SpO2), as well as the frequency of intra -operative hypotension, and the applications of ephedrine and atropine were recorded respectively at the beginning of surgery , the 30 th minute during surgery , the end of surgery and 24 hours after the surgery.Results The operations were all successful , and no adverse reactions occurred.MAP in treatment group at the 30th minute during surgery was higher than in the control group , while it was lower than of the control group at the end of surgery ( P<0.01).HR in the treatment group (68.25 ±7.35) times· min-1 was lower than that of the control group (73.28 ±10.43)times· min-1 at the end of surgery (P<0.05 ).Conclusion Shenfu injection helps stabilize blood pressure and heart rate of patients receiving carotid artery stenting through the two-way adjustment , and it could reduce the occurrence of cerebrovascu-lar accident during the per -operative period.