BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL⁻¹ coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L⁻¹, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.

The inclusion complex of taxifolin(TAX)with hydroxypropyl-β-cyclodextrin(HP-β-CD)was prepared by saturated aqueous solution method,and the preparation conditions such as molar ratio,volume ratio of solution,inclusion temperature and inclusion time were selected by single-factor experiment.The orthogonal design of three-level four-factor L9(34)was used to screen the preparation process of the inclusion complex,and the inclusion complex was prepared with optimal preparation process.The prepared inclusion complex was characterized by scanning electron microscopy(SEM),nuclear magnetic resonance(1H NMR,2D NMR),Fourier transform infrared spectroscopy(FT-IR),ultraviolet-visible(UV-Vis)absorption spectroscopy and X-ray powder diffraction(XRD).The inclusion ratio,biostability,solubility and in vitro release of the inclusion complex were investigated.The results of orthogonal experiments showed that the optimum conditions for preparation of the inclusion complex were as follows:the molar ratio of TAX to HP-β-CD was 1:1,the volume ratio of methanol to ultra-pure water was 1:8,the inclusion time was 8 h,and the inclusion temperature was 30℃.Under the optimal conditions,the inclusion ratio between TAX and HP-β-CD was calculated to be 1:1 by Job's curve method.According to the change of UV-vis absorption spectra,the host-guest complexation constant of 4.9488×104 L/mol was obtained by Benesi-Hildebrand curve method.The solubility of TAX increased from 1.2665 mg/mL to 19.3469 mg/mL after inclusion,demonstrating that HP-β-CD could serve as an effective host molecule for TAX,which could significantly enhance the bio-stability and solubility of the formed inclusion complex.

Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7％)and 30 females(30.3％),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P＞0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1％[41/46]vs.69.8％[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P＞0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P＜0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P＜0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P＜0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5％(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5％(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P＞0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5％[43/46]vs.77.4％[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P＞0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5％[3/46]vs.20.8％[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.

Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.