BACKGROUND:Ossification of the ligamentum flavum was previously considered to be rare in the population.As research has progressed,its incidence rate is increasing gradually,which has aroused the interest of a large number of researchers. OBJECTIVE:To visualize and analyze the research results on ossification of the ligamentum flavum from the Web of Science Core Collection since 1999 using bibliometric methods,and to review the research history of ossification of the ligamentum flavum,highlighting important literature,summarizing research hotspots,and providing ideas for researchers to find research directions. METHODS:Using the Web of Science Core Collection as the data source,relevant papers on ossification of the ligamentum flavum were searched and screened.VOSviewer 1.6.19 and CiteSpace 6.2.R6 were used to conduct the visual analysis of annual publication volume,research countries,institutions,citations,journals,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 347 papers were included.Since 1999,the number of published papers has increased in a spiral pattern.China's research started later than Japan's,but the number of publications has come up later,with Peking University being the institution with the most publications,and Prof.Chen Zhongqiang from Peking University being the scholar with the most publications.(2)Five of the 10 most frequently cited publications were related to the surgical treatment of the disease.(3)Excluding keywords directly related to the research topic and synthetically analyzing frequencies and betweenness centralities of key words,terms such as"thoracic myelopathy,""dural ossification,""minimally invasive surgery,"and"ossification of the posterior longitudinal ligament"occupied a central position in this field.(4)Keywords clustering analysis showed that clinical manifestations and surgical treatment of ossification of the ligamentum flavum accounted for a large proportion of study.(5)The timeline and burst analysis of keywords revealed that"minimally invasive surgery"appeared as a keyword around 2015,with the highest burst strength and the latest burst start time,and began to receive extensive attention from researchers in 2019.The burst of the keyword"dural ossification"has not yet ended.(6)Surgical treatment for ossification of the ligamentum flavum has been at the forefront of research.Development and research of minimally invasive surgery and research on dural ossification secondary to ossification of the ligamentum flavum are both current research hotspots and possible future research trends.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

Guided by the concept of "blood-pulse-heart-spirit"， it is believed that stable angina combined with insomnia is caused by disturbance of blood vessels， which leads to loss of nourishment for the heart body and heart spirit， so the core treatment principle is to regulate the blood vessels and calm the mind. At the beginning of the disease， it shows as the liver fails to govern the free flow of qi， and disorders qi and blood； during the progress of the disease， it shows as spleen deficiency and phlegm stagnation， phlegm and blood stasis obstructing the vessels； the central mechanism of the disease shows as disturbance of blood vessels and insufficient heart yin. For the pattern of liver depression and blood stasis， pattern of phlegm and blood stasis blocking the vessels， and pattern of heart yin deficiency， it is recommended to treat by Wuzang Shenning Formula （五脏神宁方） to dredge the liver and regulate the vessels， Banxia Houpo Decoction （半夏厚朴汤） plus Gualou Xiebai Banxia Decoction （瓜蒌薤白半夏汤） to dissolve phlegm and regulate the vessels， and Yunpi Tiaoxin Decoction （运脾调心汤） to nourish the yin and regulate the vessels. Throughout the treatment， pattern differentiation and treatment is accompanied by the method of calming the mind with heavy sedatives and nourishing the blood to calm the mind， so as to achieve the purpose of regulating mind and heart together and treating the body and spirit at the same time.

AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.

Objective:To evaluate the clinical efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）in children with severe aplastic anemia（SAA）.Methods:Twenty-seven cases with SAA who had been treated with allo-HSCT from January 2020 to December 2022 were retrospectively analyzed and reviewed.Results:（1）A total of 27 SAA patients were enrolled，including 18 males and 9 females，with a median age of 8 (2-15) years.There were 20 cases of SAA-Ⅰ type,7 cases of SAA-Ⅱ type.Based upon donor sources，three cases of matched sibling donors hematopoietic stem cell transplantation,and 24 cases of haploidentical hematopoietic stem cell transplantation were adopted.（2）Hematopoietic reconstruction was achieved in all 27 cases.The median implantation time of neutrophils and platelets was 10（9-20）days and 12（7-26）days respectively.The cumulative incidence of acute graft-versus-host disease（GVHD）was 66.67%（18/27）.The incidence of grade Ⅰ-Ⅱ was 55.56%（15/27）and that of grade Ⅲ-Ⅳ was 11.11%（3/27）.The incidence of chronic GVHD was 7.41%（2/27）.Transplant-associated thrombotic microangiopathy (TA-TMA) occurred in 7.41%（2/27）patients,cytomegalovirus viremia in 62.96%（17/27）patients,epstein-barr virus infection in 33.33%（9/27）patients,and 14.81%（4/27）patients progressed to post-transplant lymphoproliferative disorder (PTLD).（3）The median follow-up time was 12 (2-28) months.The overall survival rate was 96.29%.Twenty-six patients survived,and one patient died due to multiple complications of severe acute GVHD,TA-TMA,cytomegalovirus infection,PTLD and secondary epilepsy.Conclusion:Allo-HSCT is an effective therapy for SAA in children.The effective rate of this research is 96.29%.Acute GVHD is still the key to therapy.The incidence rate of acute GVHD is 66.67% in this study.The blood incompatibility of donor and recipient may affect the incidence of GVHD.The intensity of GVHD prevention should be reduced after HLA-matched sibling donor-hematopoietic stem cell transplantation so as to avoid the complications of virus recurrence and PTLD.

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Objective To investigate the effect of injection volume on clinical efficacy after minimally invasive puncture and drainage in the treatment of moderate basal ganglia cerebral hemorrhage underlying controlling the dosage of drugs in the elderly.Methods After successfully inserting the puncture needle into the center point in the largest layer long axis,the liquid hematoma was aspirated,and 40,000 units urokinase was injected into the hematoma cavity twice a day(2 mL in the small volume Group(SG),and 4 mL in the large volume group(LG),respectively).The needle were then adjusted and removed according to the hematoma clearance.The clearance rate of hematoma,intracranial pressure,edema volume,mortality,incidence of complications,neurological deficit score(NDS)and activities of daily living(ADL)were compared and analyzed.Results There were no significant differences in the first hematoma clearance rate,postoperative ICP and mortality between the two groups(P>0.05).Comparing to the SG,there was a relative higher postoperative hematoma clearance rate and lower volume of perihematoma edema in the LG(P<0.05).Meanwhile,the needle retention time,urokinase usage and cumulative complications at 28 days after operation were lower than in the SG(P<0.05).For two parameters representing long-term outcome,the NDS and ADL scores were much better in LG than in SG(P<0.05).Conclusion Large volume injection can effectively drain the hematoma,shorten the needle retention time,reduce the usage of urokinase,decrease the incidence of postoperative complications and improve the prognosis of patients,thereby providing effective and safe method in treating moderate basal ganglia cerebral hemorrhage in the elderly.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective: To understand the prevalence rate of pre myopia among preschoolers and its associated factors, so as to provide a basis for the formulation of myopia prevention and control policies. Methods: In May 2022, a tatol of 1 070 preschoolers in the Science City Area of Mianyang City were selected by using a cluster sampling method. The visual acuity of preschool children was obtained through refractive examination, and a questionnaire survey was conducted to investigate associated factors of myopia in the preclinical stage by Chi square test and multivariate Logistic regression analysis. Results: The prevalence rate of pre myopia in preschoolers was 67.01%, including 66.30% for boys and 67.76% for girls. There was no significant difference by sex( χ 2=0.26, P > 0.05). Multivariate Logistic regression analysis showed that at least one parent with myopia, too much near work activities, time spent on outdoor activity <2 h per day, lack of sleep, and screen time ≥1 h per day were positively correlated with the occurrence of pre myopia( OR =1.62, 1.46, 1.46, 1.38, 1.53, P <0.01). Conclusion The prevalence of pre myopia among preschool children in Science City Area is high. It is suggested that parents, kindergartens and relevant departments should pay attention to the visual status of preschoolers, increase outdoor activities, ensure adequate sleep and train preschoolers to develop scientific eye hygiene habits.