Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

A porous composite scaffold is prepared through freeze-drying method using sodium alginate as the matrix and calcium citrate double salt as the functional enhancer.To thoroughly investigate the structure and properties of the composite scaffold,advanced instruments including Fourier transform infrared spectrometer,X-ray diffractometer,scanning electron microscope,and thermogravimetric analyzer are utilized for comprehensive structural characterization.Meanwhile,key properties such as porosity,mechanical performance,swelling ratio,gel fraction,and in vitro degradation rate are systematically tested and analyzed.The results show that the composite of sodium alginate and calcium citrate double salt is a physical complex.The porosity of the scaffold mainly ranges from 200 to 600 μm,and as the addition of double salt increases,the pore size firstly increases and then slightly decreases,while the pore distribution become more uneven.In terms of mechanical properties,with the gradual increase of the content of double salt in the scaffold,the mechanical properties of the scaffold are significantly improved.However,its swelling ratio and gel fraction exhibit decreasing trends.Additionally,the degradation rate of the alginate scaffold is relatively fast,while the addition of calcium citrate double salt does not significantly improve the degradation rate.This study not only provides valuable insights into the preparation and property research of porous composite scaffold composed of sodium alginate/calcium citrate double salt,but also offers important reference for their potential applications in biomedicine.

A porous composite scaffold is prepared through freeze-drying method using sodium alginate as the matrix and calcium citrate double salt as the functional enhancer.To thoroughly investigate the structure and properties of the composite scaffold,advanced instruments including Fourier transform infrared spectrometer,X-ray diffractometer,scanning electron microscope,and thermogravimetric analyzer are utilized for comprehensive structural characterization.Meanwhile,key properties such as porosity,mechanical performance,swelling ratio,gel fraction,and in vitro degradation rate are systematically tested and analyzed.The results show that the composite of sodium alginate and calcium citrate double salt is a physical complex.The porosity of the scaffold mainly ranges from 200 to 600 μm,and as the addition of double salt increases,the pore size firstly increases and then slightly decreases,while the pore distribution become more uneven.In terms of mechanical properties,with the gradual increase of the content of double salt in the scaffold,the mechanical properties of the scaffold are significantly improved.However,its swelling ratio and gel fraction exhibit decreasing trends.Additionally,the degradation rate of the alginate scaffold is relatively fast,while the addition of calcium citrate double salt does not significantly improve the degradation rate.This study not only provides valuable insights into the preparation and property research of porous composite scaffold composed of sodium alginate/calcium citrate double salt,but also offers important reference for their potential applications in biomedicine.

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective To make the cost-effectiveness analysis of pembrolizumab and platinum chemotherapy as the first-line treatment for advanced non-small cell lung cancer(NSCLC)in the population with tumor proportion score(TPS)≥1%of PD-L1,and provide some reference for the clinical use and future price negotiation of pembrolizumab.Methods Based on Pubmed database,the published RCT literatures of pembrolizumab were analyzed,and the survival data were extracted,combined with the treatment plan of a tertiary hospital,the Markov model were established to simulate the cost and health effectiveness of patients for twenty years,and the stability of the model was tested by one-way sensitivity analysis and probability sensitivity analysis.Results Twenty years later,the cost-effectiveness ratio of pembrolizumab group and chemotherapy group was ￥58 517.60/quality adjusted life month(QALM)and ￥41 213.08/QALM.Compared with the chemotherapy group,the incremental cost effective ratio(ICER)was ￥104 485.36/QALM.Conclusion When the willingness to pay(WTP)value was ￥30 902/QALM,the pembrolizumab therapy was not more cost-effective advantages than platinum chemotherapy,and the sensitivity analysis showed that the results of the model were relatively stable.

Objective: To investigate the present situation of health education on school myopia prevention and control in primary and middle schools in Beijing, so as to provide scientific basis and suggestions for effective implementation of health education on school myopia prevention and control. Methods: From November 6-17, 2023, a total of 551 school doctors and health care teachers from public primary and secondary schools in seven districts of Beijing were investigated by using stratified random cluster sampling method. The contents included basic information, the basic situation of school health work, and the status of myopia prevention and control in schools. The data was described by frequency and proportion. Chisquare test was used to analyze the influencing factors. Results: A total of 89.8% of the respondents were found in the school of offering health education courses about myopia prevention and control. Among these respondents, 54.5% were equipped with health education course material of professional myopia prevention and control, and the teachers were primarily class teachers (57.6%), health care teachers (45.5%), and physical education teachers (45.1%), and most of the classes were conducted once a month (33.7%) and once a semester (28.1%). A total of 95.6% of the subjects had health education activities about myopia prevention and control at their schools. The frequency of activities was once a month (38.5%) and once a semester (27.9%). There were statistically significant differences of the report rate in setting up health education courses on myopia prevention and control, and the frequency of activities in different areas and different types of schools (χ2=19.53, 13.15, 34.30, 20.32, P<0.05). Conclusions Health education on school myopia prevention and control in primary and middle schools in Beijing is supportive. But health education courses taught by professional teachers should pay attention to the norms of the course material to complete a certain amount of class time, and development of health education activities should be diversified, so as to effectively implement health education of myopia prevention and control at school.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

ObjectiveTo explore the current status and issues regarding the application of ancient books in clinical practice guidelines and expert consensus of traditional Chinese medicine （TCM） published in China， and to provide methodological recommendations for the incorporation of ancient books in the development of TCM guidelines. MethodsWe searched China National Knowledge Infrastructure （CNKI）， WanFang Data， VIP， SinoMed， PubMed， Embase， as well as six industry websites including China Association of Chinese Medicine， National Group Standards Information Platform， and Chinese Association of the Integration of Traditional and Western Medicine，etc. TCM clinical practice guidelines or expert consensus issued during January 1st， 2017， to November 26th， 2022 were searched. Clinical practice guidelines or expert consensus that explicitly referred to ancient books were included， and the content regarding the searching for ancient books， sources of access to ancient books， methods of evaluating the level of evidence， methods of evaluating the level of recommendation， and methods of evaluating the evidence for the ancient books were analysed. ResultsA total of 1,215 TCM clinical practice guidelines or expert consensus were retrieved， with 442 articles explicitly mentioning the application of ancient books， including 300 （67.87%） clinical practice guidelines and 142 （32.13%） expert consensus. Sixty of the 442 publications explicitly reported that ancient books searching had been conducted （13.57%）； among these 60 publications 27 （45.00%） explicitly reported ancient books searching strategies， and the most frequent method was manual searching with a total of 24 articles （40.00%）. The most popular search source was Chinese Medical Dictionary， a TCM classics database， with a total of 18 articles. 197 articles （44.57%） explicitly reported the evaluation criteria for the level of evidence， of which 141 articles （71.57%） involved the evaluation criteria for the ancient books； 413 articles （93.44%） mentioned ancient books in the recommendations， and only the source of formula name was mentioned in 409 （99.03%） of the publications. ConclusionThe current application of ancient books in TCM clinical practice guidelines and expert consensus is limited， with issues of non-standard searching and evaluation methods. Standar-dization and uniformity are needed in evidence grading and recommendation standards. Future research should clarify the scope and methods of applying ancient book， emphasize their integration with modern research evidence， and enhance their value and quality in the development of TCM clinical practice guidelines.

Objectives:To evaluate the clinical efficacy and safety of percutaneous transforaminal endoscopic surgery(PTES)combined with mini-incision oblique lumbar interbody fusion(OLIF)and screw-rod fixation un-der local anesthesia for the treatment of single-segment lumbar instability,and to compare it with minimally invasive surgery-transforaminal lumbar interbody fusion(MIS-TLIF).Methods:A total of 68 patients with sin-gle-segment lumbar instability and neurological symptoms who were treated in the Department of Orthopedics at Zhongshan Hospital,Fudan University,between June 2017 and April 2019 were retrospectively analyzed.Of the patients,33 underwent PTES combined with mini-incision OLIF and screw-rod fixation(PTES+OLIF,Group A,20 males and 13 females;age 59.4±8.0 years;L3/4 4 cases,L4/5 29 cases),while the other 35 under-went MIS-TLIF(Group B,22 males and 13 females;age 61.2±7.5 years;L3/4 4 cases,L4/5 31 cases).There were no significant differences between the two groups in terms of age,sex ratio,or level of involvement.The operative time,blood loss,incision length,fluoroscopy times,and length of hospital stay were compared be-tween the two groups.Visual analog scale(VAS)scores for back pain and leg pain were recorded and com-pared at preoperation,immediate postoperation,1 month,2 months,3 months,6 months,1 year,and 2 year time points.The Oswestry disability index(ODI),intervertebral space height(ISH),lumbar lordosis(LL),surgical segment lordosis angle(SLA),intraoperative and postoperative complications,and fusion grade according to the Bridwell classification were also compared and evaluated at preoperation,immediate postoperation,and postop-erative 2 years.Results:Both groups of patients successfully completed the surgeries without intraoperative complications.The operative time was 49.5±7.6min for PTES under local anesthesia,and 75.3±13.1min for O-LIF under general anesthesia in group A,while it was 103.9±17.6min for MIS-TLIF under general anesthesia in group B.The intraoperative blood loss was 30mL(range 15-110mL)in group A and 80mL(range 50-310mL)in group B.The incision length was 8.0±1.2mm for PTES,and 39.0±3.3mm for OLIF in group A;The inci-sion length was 41.5±2.8mm for MIS-TLIF in group B.The number of fluoroscopy was 6(range 5-8)for PTES and 7(range 5-10)for OLIF in group A,and 7(range 6-11)in group B.The length of hospital stay was 4d(range 3-5d)in group A and 7d(range 6-10d)in group B.Both groups were followed up for 2 years.Compared with preoperative levels,the VAS scores for back and leg pain,and ODI were significantly de-creased at all postoperative time points(P＜0.05)in both groups.The immediate postoperative VAS score for back pain in group A was significantly lower than that in group B(P＜0.000).However,at subsequent time points,no significant differences in VAS scores for back and leg pain,or ODI were found between the two groups(P＞0.05).The ISH and SLA at immediate postoperation in group A were significantly higher than those in group B(P=0.018,P=0.002).At 2 years'follow-up,the ISH in group A remained significantly higher than that in group B(P=0.004).There was no significant difference in LL between the two groups at all postopera-tive time points(P＞0.05).25 cases(75.8％)in group A achieved grade I fusion,and 8 cases(24.2％)achieved grade n fusion;In group B,21 cases(60.0％)achieved grade Ⅰ fusion,and 14 cases(40.0％)achieved grade n fusion.There was no significant difference in the fusion grade between the two groups(P=0.126).One pa-tient in group A developed hip flexion pain and weakness,which resolved at 3d after operation.Two cases of dural tear with cerebrospinal fluid leakage occurred in group B,without neurological symptoms,and resolved after drainage tube removal at 7d postoperatively.No incision infections,permanent nerve damage,major vas-cular injury,implant loosening,or subsidence were observed.The postoperative complication rate was not sig-nificantly different between the two groups(2.8％vs 5.7％,P=0.590).Conclusions:Compared with MIS-TLIF for the treatment of single-segment lumbar instability,PTES combined with mini-incision OLIF and screw-rod fixation offers smaller trauma,less blood loss,shorter general anesthesia duration,faster relief of back pain,and better recovery of ISH and SLA.PTES combined with mini-incision OLIF and screw-rod fixation is an excellent choice for treating patients with lumbar instability who need direct decompression.