The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective To evaluate the clinical efficacy of Targeted Ⅱ Formula(composed of Astragali Radix,Pseudostellariae Radix,Ophiopogonis Radix,Asparagi Radix,Glehniae Radix,Rehmanniae Radix,Ligustri Lucidi Fructus,Ecliptae Herba,Polygonati Rhizoma,Polygonati Odorati Rhizoma,etc.)in delaying epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)resistance in EGFR mutation-positive non-small cell lung cancer(NSCLC)patients with.Methods Between January 1,2019 and June 30,2023,64 NSCLC patients with qi-yin deficiency syndrome treated at Shanghai Pulmonary Hospital(affiliated to Tongji University)were stratified based on their 1-month post-targeted therapy response and then were randomized into a treatment group(receiving Icotinib plus Targeted Ⅱ Formula decoction)or a control group(receiving Icotinib alone).Patients were followed-up until disease progression.Progression-free survival(PFS),adverse events,quality of life,and immune function were assessed.Results(1)In terms of PFS,the mean PFS in the treatment group was(18.78±7.17)months,while that in the control group was(11.76±4.26)months.The PFS in the treatment group was significantly longer than that in the control group,with a statistically significant difference(P＜0.001);the 1-year PFS rate in the treatment group was 87.50％(28/32),significantly higher than the 38.71％(12/31)in the control group,with a statistically significant difference(P＜0.001).(2)In terms of adverse reactions,the incidence of targeted drug-related rash in the treatment group was 68.75％(22/32),lower than that of the control group(80.65％,25/31),but the difference between the two groups was not statistically significant(P＞0.05).In terms of rash grading,both groups primarily had Grade 1 rashes,and the treatment group had fewer Grade 2 and 3 rashes than the control group,indicating that the severity of rashes was more pronounced in the control group.(3)In terms of quality of life,after treatment,the Karnofsky Performance Status(KPS)score in the treatment group significantly increased compared to before treatment(P＜0.05),while the control group showed no significant increase compared to before treatment(P＞0.05).The intergroup comparison revealed that the increase of KPS scores in the treatment group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(4)In terms of immune function,after treatment,the levels of CD8+T lymphocytes and interferon-γ(IFN-γ)in peripheral blood were significantly higher in the treatment group than before treatment(P＜0.05),while those in the control group were significantly lower than before treatment(P＜0.05);Intergroup comparisons revealed that the treatment group exhibited a significantly greater reduction in peripheral blood CD8+T lymphocyte and IFN-γ expression levels compared to the control group,with statistically significant differences(P＜0.05).Conclusion This study employed an innovative stratified randomization design to eliminate bias in Icotinib efficacy.The results demonstrate that Targeted Ⅱ Formula effectively delays EGFR-TKI resistance,mitigates adverse events,and improves quality of life in EGFR mutation-positive NSCLC patients with qi-yin deficiency syndrome,supporting its role as an adjuvant therapy in targeted lung cancer treatment.

AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.

Objective To develop a novel micro-extraction procedure based on polystyrene nanofibers as solid-phase extraction sorbent to extract four atypical antipsychotics including amisulpride,olanzapine,risperidone,paliperidone from human urine samples.Methods Polystyrene nanofibers were prepared by electrostatic spinning technique,and four atypical antipsychotics in human urine were extracted by a solid phase extraction column using polystyrene nanofibers as sorbent.The detection was performed on Waters XBridge BEH C18 with the mobile phase of0.1％formic acid aqueous solution(A)-acetonitrile(B)by a gradient elution at 0.25 mL·min-1 flow rate.The temperature of column was 40 ℃ and the injection volume was 3 μL.The method's selectivity,standard curves,quantification limit,precision,accuracy,extraction recovery,matrix effect,and stability were assessed.Results The linear ranges of the four analytes were found to be 1-100 ng·mL-1,with correlation coefficients all exceeding 0.996.The lower limit of quantification was 1 ng·mL-1,and the limit of quantitation ranged from 0.01-0.10 ng·mL-1.The intra-day and inter-day RSDs for the four analytes ranged from 2.34％-14.48％,with extraction recoveries all exceeding 75.75％.The matrix effect falls within the range of 85.00％-115.00％.The stability of samples placed in the autosampler for 24 hours exhibited RSDs ranging from 2.19％-12.06％,while the stability after three freeze-thaw cycles ranged from 3.65％-13.81％.Conclusion This method is sensitive and suitable for the determination of target analytes in complex matrices,and provides a reliable analytical tool for the detection of atypical antipsychotics.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Background:Complete colonoscopy is key to the diagnosis and treatment of colorectal disease,its role in reducing the morbidity and mortality of colorectal cancer is well known.Nonetheless,there are numerous factors,not just from the endoscopist's perspective but also from the patient's,that can potentially increase the difficulty of completing a colonoscopy.Aims:To identify patient-related factors that influenced the difficulty of a colonoscopy.Methods:Through two rounds of expert consultation,the factors that might affect the difficulty of colonoscopy were selected.A total of 1621 consecutive painless colonoscopies from Jan.2021 to Jan.2022 at the endoscopy center of The Affiliated Wuxi People's Hospital of Nanjing Medical University were evaluated in a retrospective manner.Factors including demographic data,cecal insertion time,adenoma detection rate and so on were recorded.These factors were analyzed to determine their association with difficulty by using Logistic regression model.Results:A total of 29 patient-related factors affecting the difficulty of colonoscopy were selected.Through retrospective analysis,the mean age of 1621 cases was(47.45±13.27)years,of which 45.8%were male and the mean body mass index was(23.32±3.11)kg/m2.Logistic regression analysis revealed that age≥60 years(OR=2.890,95%CI:1.957-4.269,P<0.001),female gender(OR=0.324,95%CI:0.217-0.484,P<0.001),history of gynecological surgery(OR=14.895,95%CI:9.741-22.776,P<0.001),constipation for 20-30 years(OR= 1.412,95%CI:0.925-2.156,P=0.010)were independent risk factors for difficult colonoscopy.Conclusions:This retrospective study identified several patient-related factors that influence the technical difficulty of colonoscopy.These findings had implications for practice and teaching of colonoscopy.

Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96％.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P＞0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P＜0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.

Through consulting the ancient herbal and medical books， combined with the field investigation， the name， origin， collection and processing of Dendrobium medicinal materials were researched， which provided a basis for the development of famous classical formulas containing this kind of herbs. Due to the wide distribution of D. officinale， the Dendrobium species represented by D. officinale and D. huoshanense， which are short， fleshy and rich in mucus， should be the most mainstream of Dendrobium medicinal materials in previous dynasties. Compared with Shihu， Muhu with loose texture， long and hollow is born on trees. According to the characteristic description， it should be D. nobile， D. fimbriatum and so on， of which D. nobile was the mainstream. The Chinese meaning of Jinchai was confused in the past dynasties， so it was not suitable to be treated as a plant name. The production areas of Dendrobium medicinal materials in the past dynasties have changed with the discovery of varieties， artificial cultivation and other factors. Lu'an， Anhui province， was the earliest recorded in the Han and Wei dynasties. Since the Tang and Song dynasties， it had been extended to Guangdong and Guangxi， and it was considered that "Dendrobii Caulis in Guangnan was the best". In the Ming dynasty， Sichuan and Zhejiang products were highly praised， and in the Qing dynasty， Huoshan products were highly praised. Dendrobium medicinal materials had been used as medicine by stems in all dynasties. The medicinal materials were divided into fresh products and dry products. The fresh products can be used immediately after removing the sediment from the roots. The dry products need further processing， most of them used wine as auxiliary materials for steaming， simmer to paste or decoction into medicine. D. officinale and D. huoshanense have special processing specifications since the middle of Qing dynasty， that is， "Fengdou". According to the research results， in Ganluyin， the effect of Dendrobium medicinal materials is mainly heat clearing， and D. nobile with bitter taste can be selected. The main effect of Dendrobium medicinal materials in Dihuang Yinzi is tonic， D. officinale or D. huoshanense can be selected.

Atractylodis Rhizoma is a kind of commonly used clinical Chinese medicine （TCM）， which was first recorded in Shennong Bencaojing （《神农本草经》）. At that time， it was called "Zhu"， which is the general name of Atractylodis Rhizoma and Atractylodis Macrocephalae Rhizoma. After Song dynasty， Atractylodis Rhizoma and Atractylodis Macrocephalae Rhizoma were separated. Atractylodis Rhizoma can be divided into Atractylodes lancea and A. chinensis. In history， A. lancea as authentic， that its quality is better than A. chinensis. However， the quality of Atractylodis Rhizoma was evaluated by the index component atractylodin in the 2020 edition of Chinese Pharmacopoeia. The general results showed that the content of atractylodin in A. lancea was low， even failed to meet the specified standard， and its content in A. chinensis was significantly higher than that in A. lancea. The results were inconsistent with the records of ancient books and documents， and the quality theory of "genuine medicine is the best". It could not reflect the quality advantage of genuine Atractylodis Rhizoma， and may even affect the clinical application and development momentum of genuine medicine. In short， the quality standard of TCM should not only conform to the historical experience， but also have the connotation of modern science and technology， which can stand the test of practice. Based on this， the author intends to sort out relevant laws and regulations， sort out the literature related to the authenticity， composition and efficacy of Atractylodis Rhizoma， and analyze the rationality of the current standard of Atractylodis Rhizoma by integrating the relevant records of historical classics and modern research results， so as to provide a basis for the improvement of the quality standard of Atractylodis Rhizoma.