Objective To explore the action mechanism of Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib on renal fibrosis after renal ischemia-reperfusion injury (RIRI). Methods C57BL/6 mice were randomly divided into sham operation group, modeling group and modeling + zanubrutinib treatment group (zanubrutinib group), with 5 mice in each group. The groups underwent sham operation, RIRI modeling and RIRI modeling + zanubrutinib (5 mg/kg) treatment, respectively. Tissues were collected after 21 days. The morphological changes of the kidneys, histopathological changes, levels of M1 macrophages in the kidneys, inflammatory responses in the kidneys, and the expression of related inflammatory signaling pathways of macrophages induced by lipopolysaccharide(LPS) + interferon(IFN)-γ in vitro after lentivirus transfection were observed. Results Compared with the sham operation group, the kidneys of the modeling group mice shrank, the ratio of unilateral kidney weight to mouse body weight decreased, renal tubular interstitial fibrosis worsened, and the expression of α-smooth muscle actin (α-SMA) and type I collagen in the kidneys increased. The expression of F4/80 and CD86 in the kidneys increased, the lumen of the renal proximal convoluted tubules was significantly dilated, cellular debris accumulated in the lumen and inflammatory cell infiltration occurred, and the messenger RNA (mRNA) levels of CD86, tumor necrosis factor (TNF)-α, interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and IL-1β in the kidneys increased. Compared with the modeling group, the kidneys of the zanubrutinib group mice enlarged after RIRI, the ratio of unilateral kidney weight to mouse body weight increased, renal tubular interstitial fibrosis was alleviated, and the expression of α-SMA and type I collagen in the kidneys decreased. The expression of F4/80 and CD86 in the kidneys decreased, the number of CD45⁺ lymphocytes and CD11b⁺ F4/80⁺ macrophages in the kidneys decreased, the infiltration of CD11b⁺ F4/80⁺ and CD86⁺ macrophages in the damaged tissue decreased, the degree of renal inflammatory pathological changes was milder, and the mRNA levels of CD86, TNF-α, IL-6, iNOS and IL-1β in the kidneys decreased. In vitro experiments using LPS+IFN-γ to induce M1-type macrophages found that the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and nuclear factor (NF)-κB increased, while the phosphorylation levels decreased after BTK knockdown, indicating that BTK knockdown may inhibit the PI3K/Akt and NF-κB related inflammatory signaling pathways, thereby reducing the pro-inflammatory effects of LPS+IFN-γ induced M1-type macrophages. Conclusions Zanubrutinib may alleviate renal fibrosis after RIRI by inhibiting the PI3K/Akt and NF-κB related inflammatory signaling pathways, reducing the infiltration of M1 macrophages and the expression of related inflammatory factors, providing potential evidence for its clinical application.

BACKGROUND:It has been suggested that CT multiplanar reconstruction should be performed prior to the placement of axial pedicle screws to determine the anatomy of the C2 pedicle in each patient,to design the appropriate screw locus and diameter,and to evaluate the feasibility of screw placement to reduce the incidence of surgery-related complications. OBJECTIVE:To evaluate the feasibility of axis pedicle screw placement by morphologic classification of pediculoisthmic component with CT multiplanar reconstruction. METHODS:The CT data of 200 patients(400 axial pedicle screws)with cervical spine were retrospectively studied by using Siemens Syngo.Via software.According to the direction of the axis of the pedicle,the CT multiplanar reconstruction positioning line was adjusted to reconstruct the sectional image of the narrowest part of the pediculoisthmic component.According to its morphological characteristics,the narrowest part of the pediculoisthmic component was divided into three types:type 1,"hook"type:Type 1a outer diameter width(a1)>0.4 cm,type 1b outer diameter width(a1)≤0.4 cm;type 2,"like circle/ellipse"type;type 3,"horizontal ellipse"type.The outer diameter width of the narrowest part of pediculoisthmic component(d1),medullary cavity width(d2),outer diameter height(a1),and medullary cavity height(a2)were compared among the three types,and the feasibility of pedicle screw placement of the three types was evaluated. RESULTS AND CONCLUSION:(1)A total of 400 axial pedicles included 269 cases of type 1,130 cases of type 2,and 1 case of type 3.(2)The mean external diameter height between types 1 and 2 was not significantly different(P>0.05).The mean medullary cavity height,mean outer diameter widths,and mean medullary cavity width were significantly different(P<0.001).There were 42 cases(15.6%)of type 1 and 0 cases(0.00%)of type 2 with mean external diameter width≤0.4 cm,and the difference was significant(P<0.001).There was only one case of type 3,whose external diameter height,medullary cavity height,outer diameter width and medullary cavity width were 1.20 cm,0.84 cm,0.64 cm and 0.31 cm,respectively.(3)These results confirm that axial pedicle screws can be safely inserted in patients with types 1a,2 and 3,which requires no further measurement and assessment.Pedicle screw insertion should be performed with caution in type 1b patients.Therefore,in type 1 patients,the width of the narrowest outer diameter of the pediculoisthmic component should be further measured to evaluate the feasibility of axial pedicle screw placement.

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder.Primarily involving the skin and central nervous system, it also impacts the heart, lungs, kidneys, and other organs.The vast majority of TSC patients may experience neuropsychiatric symptoms during their lifetime, including behavioral, mental, intellectual, academic, neuropsychological, and psychosocial disorders, which are collectively referred to as TSC-associated neuropsychiatric disorders(TAND).The TAND Checklist is a screening tool designed to identify potential neuropsychiatric disorders by facilitating dialogues between TSC patients, their families, and clinicians.This article focuses on the concept and research history of TAND and the application of the TAND Checklist, contributing to the comprehensive and systematic clinical evaluation and understanding of the prognosis of children with TAND.

Objective To explore the candidate genes and potential molecular mechanisms of anti-neutrophil cyto-plasmic antibodies(ANCA)-associated vasculitis by bioinformatics and experimental validation,and to provide a scientific theoretical basis for the treatment of potential inflammatory targets for ANCA-associated vasculitis.Meth-ods The GSE108109 chip data was retrieved from the Gene Expression Omnibus(GEO)database,and the differ-ential genes were processed,analyzed and screened using the R language related program package.Kyoto encyclo-pedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analysis was carried out using DAVID online network cable,and the interaction network of the protein encoded by the selected genes of inflammatory syn-drome was constructed through STRING website.Further endogenous competitive RNA(ceRNA)regulatory net-work was predicted and constructed through miRWalk and DIANA-LncBase databases,and key genes were screened from the network to draw ROC curve.The renal biopsy samples of patients with ANCA-associated vasculi-tis confirmed by our hospital were collected as the experimental group,and the renal biopsy samples of IgA ne-phropathy and micro-adaptive nephropathy were collected as the control group.Immunohistochemical staining was performed on the collected renal biopsy samples,and the average optical density was calculated by semi-quantita-tive analysis of immunohistochemical staining to further verify the expression of the key genes screened by the bioin-formatics analysis.Pearson linear correlation analysis was performed between the average optical density results and the clinical inflammatory data of patients.Results 846 differential genes were screened,of which 444 genes were significantly up-regulated and 402 genes were significantly down-regulated.Through KEGG and GO analysis,im-portant differentially expressed genes related to inflammation regulation were obtained.Among them,CSF1R and TNFRSF1B,two differentially expressed genes never reported in ANCA-associated vasculitis,attracted our atten-tion.At the same time,we constructed multiple ceRNA regulatory axes including KCNQ1OT1-hsa-miR-125a-5p-TNFRSF1B.There were 15 samples of ANCA-associated vasculitis,6 samples of IgA nephropathy,and 3 samples of micropathological kidney.Immunohistochemical results of renal biopsy specimens showed that the expression of CSF1R and TNFRSF1B in ANCA-associated vasculitis kidney tissue was higher than that in the control group.Pearson correlation analysis of clinical data of patients in ANCA group showed that the expression of CSF1R was positively correlated with the content of neutrophil count(r=0.587),and the expression of TNFRSF1B was posi-tively correlated with the content of serum C-reactive protein(r=0.646).Conclusion Key genes related to in-flammatory regulation such as CSF1R and TNFRSF1B were investigated by bioinformatics methods,and a rigorous ceRNA regulatory network was constructed.The expression of CSF1R and TNFRSF1B in ANCA vasculitis was high-er than that in the control group through immunohistochemistry.The results provides a scientific theoretical basis for the molecular mechanism of inflammation,and laid a good foundation for new therapeutic targets of ANCA-related vasculitis for inflammation.

Objective:To analyze the clinical characteristics, treatment, and prognosis of ectopic bronchogenic cysts in children.Methods:A retrospective analysis was conducted on the data including the clinical characteristics, auxiliary examination and treatment of 21 children with ectopic bronchogenic cysts diagnosed pathologically at Children′s Hospital Affiliated to Zhengzhou University from July 2015 to December 2023. There were 16 males and 5 females, with a male-female ratio of 3.2∶1, and the age ranged from 4 days to 8 years old (median age 2 years and 8 months).Results:Among the 21 cases of ectopic bronchogenic cysts, 11 cases were found in the pharynx, with symptoms including dyspnea (4 cases), snoring during sleep (3 cases), and choking on milk(4 cases).Ten cases were found in the head, neck or anterior chest, 5 of these cases had infection history, and 5 showed progressive mass growth.Imaging and endoscopy showed 9 patients underwent preoperative color ultrasonography revealed cystic masses with well-defined boundaries. CT examination was performed on 13 patients, which showed round or nearly round masses with homogeneous density, smooth margins, and regular cyst walls. CT attenuation values ranged from 2 to 52 Hounsfield Units (HU). Four cystic lesions were assessed via MRI, 3 cases demonstrated long T1 and long T2 signals, while 1 case had a slight short T1 and long T2 signal, with high signal intensity on fat-suppressed images. Eleven cases of pharyngopharyngeal cysts were examined by electronic nasopharyngoscopy. The cysts appeared as spherical or ovoid masses with smooth surfaces, close to or slightly light in color with the surrounding tissue, with one cyst presenting with a bluish blue in the oropharynx. All 11 pharyngeal cysts were excised using low-temperature plasma under general anesthesia and intubation assisted by a nasal endoscope. The cysts were pulled and excised as completely as possible.Ten cases of neck and anterior chest cysts were completely excised. Postoperative histopathology confirmed bronchogenic cyst. Twenty-one children were followed up postoperatively for 4 months to 7 years without recurrence, except for 1 patient who was lost to follow-up.Conclusions:Ectopic bronchogenic cysts are uncommon and lack of typical imaging and clinical features.Combination of ultrasonography, CT and MRI is recommended for cases occuered in neck and anterior chest, while electronic nasopharyngoscopy complements pharyngeal evaluations. Surgical intervention is the preferred treatment choice for this disease.

Objective To investigate current situation and the influencing factors of disease distress suffered by patients with inflammatory bowel disease hence to provide a foundation for intervention.Methods A total of 240 patients with inflammatory bowel disease who visited or were hospitalized in two Grade III and Class A hospitals from January 2021 to December 2022 were selected as research subjects.General information questionnaire,inflammatory bowel disease distress scale(IBD-DS),social support rating scale(SSRS),general self-efficacy scale(GSES),were used in the survey among the patients.Multiple linear regression were used to explore the influencing factors.Results IBD-DS scores among 235 patients were found from 65 to 93,with an average of 75.8±4.9,at a medium to low level.Pearson correlation analysis and multiple linear regression revealed that marital status,disease duration,SSRS scores,GSES scores and disease activity were the independent risk factors in disease distress,toally explaining 83.6%its variance(P<0.01).Conclusion Patients with inflammatory bowel disease generally suffer a moderate to low level of disease distress.It is necessary to focus on the patients who are unmarried,have a long course of disease,have low social support and self-efficacy,and have high disease activity,and take targeted measures to reduce their disease suffering.

Objective:To discuss the method for establishing the rat models of irritable bowel syndrome(IBS)by chronic water avoidance stress(WAS)method,and to evaluate its feasibility.Methods:Thirty male Wistar rats were randomly divided into control group(n=10)and model group(n=20).The rats in model group were induced by WAS method for 1 h everyday,lasting for 10 consecutive days;the rats in control group underwent no interventions.After modeling,the general conditions and body weights of the rats in two groups were observed and recorded.The elevated plus maze(EPM)test was used to detect the percentages of the number of open arm entries(OE)and the time spent in open arms(OT)of the rats in two groups;the abdominal withdrawal reflex(AWR)test was used to assess the visceral sensitivity of the rats in two groups;electrocardiography was used to detect the heart rate variability(HRV)of the rats in two groups;electromyography(EMG)of the external oblique muscle was used to detect the colorectal pain sensitivity thresholds of the rats in two groups;multi-channel physiological signal recorder was used to monitor the slow wave frequency of the colon of the rats in two groups.Results:There were no death rats in both groups during the modeling period.After modeling,the rats in model group exhibited poor mental status,reduced spontaneous activity,hypoactivity,disordered and dull fur,irritability,and unclean anal areas;whereas,the rats in control group showed no significant changes in the mental state,spontaneous activity,fur,and perianal area.Compared with control group,the body weight of the rats in model group was significantly decreased(P<0.05).The EPM test results showed that compared with control group,the OE percentage and OT percentage of the rats in model group were significantly decreased(P<0.01).The AWR test results showed that 12 rats in model group scored≥3 points,indicating that the successful rate in creating the visceral pain models was 60%.Compared with control group,the low frequency(LF)signals and the ratio of LF/high frequency(HF)of the rats in model group were significantly increased(P<0.01),and the HF was significantly decreased(P<0.05).The EMG results showed that compared with control group,the coloretal pain sensitivity threshold of the colon of the rats in model group was significantly decreased(P<0.01),and the slow wave frequency of the colon was significantly increased(P<0.01).Conclusion:The WAS method for establishing the rat model of IBS effectively demonstrates the changes in behavior and mental state,increased the visceral sensitivity,accelerated colonic slow wave frequency,and autonomic nervous system imbalance;the WAS method can serve as an effective modeling approach for observing and evaluating the related drugs and interventions on treatment of IBS.

Objectives:To investigate the effects on the efficacy of posterior cervical laminoplasty in patients with cervical spondylotic myelopathy of different C7/T1 foraminal areas before surgery.Methods:76 patients who underwent posterior cervical open-door expansive laminoplasty for cervical spondylotic myelopathy in our hospital from September 2021 to September 2022 were analyzed retrospectively,including 58 males and 18 females,aged 64.4±8.5 years old.The area of C7/T1 foramina of patients was measured on the double oblique X-ray images before operation,and the patients were divided into two groups on the basis of the av-erage C7/T1 foraminal area:Group A,C7/T1 foraminal area ≤average value(40 patients),and group B,C7/T1 foraminal area＞average value(36 patients).The operative time and intraoperative bleeding were collected and compared between groups,and the Japanese Orthopaedic Association(JOA)scores before surgery,3 months af-ter surgery,and 12 months after surgery were obtained to calculate the JOA score improvement rate;The axi-al symptoms at 12 months after surgery were recorded,and T test,analysis of variance,and chisquare test were used to analyze whether different preoperative C7/T1 forminal areas of patients affected the efficacies after posterior cervical laminoplasty.Results:The foraminal areas of C7/T1 was 35.2±9.7mm2 in group A and 65.7±13.1mm2 in group B,and C2-C7 Cobb angle before operation was 14.0°±3.6° in group A and 16.0°±5.5° in group B,with statistical differences respectively(P＜0.05).Group A was not significantly different from group B in terms of intraoperative bleeding(176.8±88.2mL vs 183.6±100.2mL)and operative time(127.5±23.6min vs 120.3±32.6min)(P＞0.05).The JOA scores of group A and group B were 10.9±2.0 and 10.3±2.1 before operation,without statistical difference(P＞0.05);The JOA scores of group A and group B were 12.8±1.5 and 14.0±2.2 at postoperative 3 months and 14.1±1.5 and 15.9±1.7 at 12 months after operation,with statistical differences respectively(P＜0.05).There were statistical differences in the improvement rates of JOA scores between the two groups at postoperative 3 months and 12 months,respectively(P＜0.05).The incidence of axial symptoms 12 months after operation in group A and group B was 42.5％and 19.4％,respectively,with statistical difference(P＜0.05).Conclusions:Patients with larger C7/T1 foraminal area have better postoperative neurological recovery,higher rate of JOA improvement,and lower incidence of postoperative axial symptoms.