Objective To investigate the role of lipopolysaccharide(LPS)in regulating the inflammatory response of neutrophil through the leucine-rich α-2 glycoprotein 1(LRG1)/Rho-associated protein kinase(ROCK1)signaling.Methods HL-60 cells were treated with 1 μmol/L all-trans retinoic acid(ATRA)and 12.5 μL/mL dimethyl sulfoxide(DMSO)for 72 h and 96 h,and the morphological changes were observed by Wright-Giemsa staining.The expression of CD11b was detected by flow cytometry.LPS induced the activation of dHL-60 and human peripheral blood neutrophils.The transcription and secretion levels of LRG1,ROCK1 and inflammatory cytokines were detected by qPCR and ELISA,respectively.The expression levels of LRG1 and ROCK1 after the activation of dHL-60 were detected by Western blotting.Furthermore,dHL-60 was treated with the recombinant protein LRG1 and ROCK1 inhibitor Y-27632;the transcription levels of inflammatory cytokines were detected by qPCR.Results Neutrophils were activated by LPS.The expression levels of LRG1 and ROCK1 were significantly increased,and the transcription levels of inflammatory cytokines were significantly increased.The recombinant protein LRG1 activated dHL-60 in vitro,and the transcription levels of ROCK1 and inflammatory cytokines were significantly increased.Using the ROCK1 inhibitor Y-27632,the production levels of inflammatory cytokines were significantly reduced.Conclusion LPS can regulate the production levels of neutrophil inflammatory cytokines through activating the LRG1/ROCK1 signaling,thus exacerbating the inflammatory response.

Objective To explore the value of controlling nutritional status(CONUT)score and related inflammatory indicators in predicting the prognosis of clear cell renal cell carcinoma(ccRCC)patients,to provide a reference for better clinical assessment and individualized treatment plan.Methods A retrospective study was conducted on 132 patients with ccRCC admitted to four comprehensive hospitals in Yibin during 2010 and 2018.Patients'medical and follow-up records were collected,and receiver operating characteristic(ROC)curve was drawn to analyze the area under the curve(AUC)and optimal cut-off value of CONUT score and related indicators.Survival curve was plotted with Kaplan-Meier method,and the influencing factors of prognosis were analyzed with Log-rank test and Cox regression.Results During the follow-up of 62(53,71)months,37(28.03％)deaths occurred.The disease-specific survival(DSS)and progression-free survival(PFS)were 51(41,58)and 46(35,56)months,respectively.The 3-year and 5-year DSS and PFS were 84.09％and 71.97％,and 75.00％and 71.97％,respectively.The AUC of CONUT score,neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and lymphocyte to monocyte ratio(LMR)were 0.980,0.905,0.899 and 0.884,respectively,with the optimal cut-off values of 3.50,3.19,89.07 and 3.56,respectively.Cox regression showed that CONUT score(HR=0.042,95％CI:0.013-0.140)and PLR(HR=0.182,95％CI:0.045-0.744)were associated with DSS;CONUT score(HR=0.029,95％CI:0.010-0.086)and LMR(HR=2.984,95％CI:1.227-7.258)were associated with PFS.Conclusion The prognosis of ccRCC patients is related to their nutritional,immune,and inflammatory status.CONUT score and inflammatory factors(PLR,LMR)may be important predictors of DSS and PFS.

Objective:To prepare a humanized monoclonal antibody against periostin and establish a stable cell line.Meth-ods:Based on anti-periostin mouse monoclonal antibody developed by our laboratory,total RNA was extracted,and variable region sequences were obtained by RT-PCR amplification of VH and VL genes.The mouse antibody CDR region was transplanted into the human antibody framework receptor region,and the gene was subcloned into the expression vector PATX-GS2,and stably transfected into CHO cells.Monoclonal cell lines were obtained by MSX pressure screening and limited dilution.Results:VH and VL genes were amplified by RT-PCR,and the sequence of the light and heavy chain variable region were determined.Antibody humanization were successfully stablished by CDR transplantation method a murine antibody to a human framework,and a eukaryotic expression plasmid was constructed,which was transfected into CHO cells for expression,and human anti-periostin antibody was successfully obtained.ELISA and Western blot results showed that the humanized antibody had good anti-periostin activities and binding affinity.Conclu-sion:In this study,anti-periostin humanized monoclonal antibody has been successfully prepared,which can specifically bind to peri-ostin proteins in vivo and have biological activity,providing scientific data for the precise treatment of retinal fibrosis,tissue and organ fibrosis,and malignant tumors.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective:To construct and test the reliability and validity of an assessment scale for self-management of patients with dry eye, so as to help patients establish dry eye related health behaviors.Methods:Based on the knowledge attitude and practice theory, the initial scale was constructed on the basis of literature review and qualitative interview, and revised through Delphi expert consultation and expert argumentation. After the preliminary investigation, 211 dry eye patients treated in the dry eye nursing outpatient department of Beijing Tongren Hospital from August 2023 to January 2024 were selected by convenience sampling method for questionnaire investigation to test the reliability and validity of the scale.Results:Among 211 dry eye patients, there were 58 males and 153 females, aged (39.31 ± 12.81) years old. The scale of self-management of patients with dry eye included 27 items in 3 dimensions: knowledge, attitude and behavior. The authority coefficient of the two rounds of expert consultation was 0.86, and the Kendall coordination index increased from 0.175 to 0.223 (both P < 0.01). The cumulative variance contribution rates of the three dimensions were 41.843%, 54.219% and 44.273%, respectively. The Cronbach α coefficient of the scale was 0.787, and the Spearman-Brown coefficient was 0.641. Conclusions:The scale of self-management of patients with dry eye has good reliability and validity and can be used in the assessment of dry eye patients to provide a reference basis for targeted guidance and intervention.

Objective:To explore the role of information-based points system management platform in enhancing the medical management capabilities of laboratory medicine.Methods:A total of 106 personnel who were on duty from January 2021 to December 2022 in the clinical laboratory of Guangdong Provincial People′s Hospital were selected and divided into 8 professional groups, including 24 in Clinical Routine Lab, 22 in Clinical Biochemistry Lab, 11 in Clinical Immune Lab, 13 in Clinical Microbiology Lab, 10 in Clinical Molecular Lab, 9 in Flow Cytometry Lab, 9 in HuiFu Lab, and 8 in Interdisciplinary Lab. Information-based points system management platform was established by formulating the detailed rules for the assessment of this points system, and the points achieved by the 106 participants in 2021 and 2022 were obtained and analyzed. The points were divided into 6 intervals (<41, 41-45, 46-50, 51-55, 56-60 and>60).Results:The overall medical points of laboratory medicine was significantly higher in 2022 than in 2021 (52.15±5.48 vs 49.81±3.73, P<0.001). In 2022, the number of participants with points between 41-45 and 46-50 intervals was lower than those in 2021; with points 51-55, 56-60 and>60 intervals was higher than those in 2021 (χ2=10.479, P<0.05). In addition, the points of Clinical Molecular, Clinical Microbiology and HuiFu Lab were 57.46±7.40, 52.05±5.43 and 54.98±4.31 respectively, which were significantly higher than those of 2021 (50.16±4.14, 49.10±4.06, 49.23±4.28, respectively;all P<0.05). The number of report revisions has significantly decreased in 2022 (18) compared to that in 2021 (48), clinical communication and various levels of publicity and promotion were significantly increased from 52 and 58 (2021) to 108 and 137 (2022), respectively. Conclusion:The construction and application of the information-based points management system have effectively improved the enthusiasm and subjective initiative of laboratory personnel, enhanced the quality and service capabilities of laboratory medicine, and might serve as an important tool for standardized management of laboratory medicine.

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

Objective:To investigate the clinic opathological features, treatment and prognosis of children newly diagnosed with ependymoma.Methods:Clinical data of 127 pediatric ependymoma (EPN) patients (0-16 years old) treated with tumor resection and postoperative radiotherapy at Xinhua Hospital Affiliated to Shanghai Jiao Tong University between 2001 and 2021 were retrospectively analyzed. Among them, 53 children were female and 74 were male. Local control (LR), event-free survival (EFS) and overall survival (OS) rates were analyzed by Kaplan-Meier method. The relationship between clinic opathological factors and clinical prognosis, and the effect of treatment on clinical prognosis of patients were analyzed by Cox proportional hazards model.Results:At a median follow-up time of 29 months (3-251 months), the 3-year OS and EFS rates were 89.5% and 71.5%, respectively. For patients undergoing incomplete resection followed by postoperative adjuvant radiotherapy, the 3-year LR, OS and EFS rates were 78.3%, 65.8% and 85.7%, respectively. A total of 43 children were aged <3 years old when diagnosed and 84 aged ≥3 years old. The interval time between surgery and radiotherapy in children aged <3 years old was 91 d, and 35.5 d in those aged ≥3 years old ( P<0.001). For patients <3 years old, the median EFS was 90 months when initiating radiotherapy within ≤70 d after surgery, compared to 43 months for those who initiated radiotherapy at >70 d after surgery ( P=0.053). According to fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5), 39 children were classified as posterior fossa ependymoma group A (PFA group). The OS and EFS rates in the PFA group were significantly less than those in other groups (3-year OS rate were 69.2% vs. 94.6%, P<0.001; 3-year EFS rate were 46.9% vs. 79.1%, P<0.001). In the PFA group, 12 patients received postoperative adjuvant chemotherapy, 14 did not receive chemotherapy, and whether chemotherapy was given was unknown in 13 cases. No significant differences were observed in OS and EFS between patients treated with and without chemotherapy ( P=0.260, P=0.730). Univariate Cox analysis showed that tumor location and WHO CNS5 molecular classification were significantly associated with EFS, and WHO CNS5 molecular classification was significantly correlated with OS. Multivariate Cox analysis showed that tumor location in the posterior fossa was an independent risk factor for EFS ( HR=2.72, 95% CI=1.1~6.71, P=0.03). Conclusions:Patients newly diagnosed with pediatric ependymoma can obtain favorable survival after surgery combined with postoperative adjuvant radiotherapy. Patients with residual tumors can achieve favorable LC and survival after postoperative adjuvant radiotherapy. Delaying of radiotherapy tends to lead to poor survival for patients aged <3 years old when diagnosed. Children in the PFA group obtain worse prognosis compared to their counterparts in other groups. The tumor location in the posterior fossa is an independent risk factor for pediatric ependymoma.

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

Objective:To investigate the influence of clinical administration of dobutamine on blood perfusion in free flap repair of diabetic foot wounds.Methods:A prospective self‐controlled study was conducted. From January to November 2022, 20 patients with diabetic foot who met the inclusion criteria were hospitalized in the Department of Burns and Plastic Surgery of Affiliated Hospital of Zunyi Medical University, including 9 males and 11 females, aged from 44 to 75 years, with the foot wounds area ranging from 5 cm×4 cm to 20 cm×10 cm, which were repaired by free anterolateral thigh flaps. Heart rate (HR) and mean arterial pressure (MAP) were recorded before anesthesia induction, 10 minutes after vascular recanalization, when the target blood pressure (i.e., MAP being 6-10 mmHg (1 mmHg=0.133 kPa) higher than that before anesthesia induction) was reached after infusion of dobutamine, and 10 minutes after tracheal catheter removal. Additionally, indocyanine green, a contrast agent, was injected intravenously at 10 minutes after vascular recanalization and when the target blood pressure was reached after infusion of dobutamine to assess flap blood perfusion using infrared imager, and the area ratio of flaps with hyperperfusion and hypoperfusion was calculated. Other recorded variables included flap harvesting area, surgical duration, total fluid infusion amount, infusion dose and total usage of dobutamine, intraoperative adverse events, postoperative flap complications, and follow‐up outcomes. Data were statistically analyzed with paired sample t test, analysis of variance for repeated measurement, Bonferroni method, and generalized estimating equation. Results:Compared with those before anesthesia induction, HR and MAP of patients were significantly decreased at 10 minutes after vascular recanalization ( P<0.05), while HR and MAP of patients were significantly increased when the target blood pressure was reached after infusion of dobutamine ( P<0.05). Compared with those at 10 minutes after vascular recanalization, HR and MAP of patients were significantly increased when the target blood pressure was reached after infusion of dobutamine and at 10 minutes after tracheal catheter removal ( P<0.05). Compared with those when the target blood pressure was reached after infusion of dobutamine, HR and MAP of patients were significantly decreased at 10 minutes after tracheal catheter removal ( P<0.05). The area ratio of flaps with hyperperfusion of patients was 0.63±0.11 when the target blood pressure was reached after infusion of dobutamine, which was significantly higher than 0.31±0.09 at 10 minutes after vascular recanalization ( t=-9.92, P<0.05). The area ratio of flaps with hypoperfusion of patients was 0.12±0.05 when the target blood pressure was reached after infusion of dobutamine, which was significantly lower than 0.45±0.10 at 10 minutes after vascular recanalization ( t=17.05, P<0.05). The flap harvesting area of patients was (174±35) cm2, the surgical duration was (372±52) min, the total fluid infusion amount was (2 485±361) mL, the infusion dose of dobutamine was 3-13 μg·kg?1·min?1, and the total usage of dobutamine was 5.7 (2.1, 9.7) mg. Two patients showed a significant increase in MAP during the infusion of dobutamine compared with that at 10 minutes after vascular recanalization, but before reaching 6 mmHg higher than that before anesthesia induction, their HR had reached the maximum (over 130 beats/min). The HR gradually returned to around 90 beats/min after the infusion of dobutamine was stopped. On post operation day 2, one patient had partial necrosis at the distal part of the flap, which was repaired by transplantation of thin split-thickness skin graft from the opposite thigh. During the follow‐up of 3 to 6 months after operation, all the flaps survived well, with soft texture and well-formed shape, and no adverse cardiovascular events of patients were reported. Conclusions:The administration of dobutamine in free flap repair of diabetic foot wounds can significantly improve the MAP of patients, expand the area of hyperperfusion, reduce the area of hypoperfusion, and enhance the flap viability, with promising short‐term follow‐up results, which is suitable for promotion in clinical applications.