Changes of the meibomian gland in a mouse model of aqueous deficient dry eye / 中国组织工程研究

BACKGROUND:In recent years,increasing studies have focused on the abnormal proliferation and differentiation of acinous cells in the meibomian gland,suggesting that this process is closely related to the occurrence and development of dry eye.Structural and functional abnormalities such as blockage of the lumen of the meibomian gland and atrophy of the glands can cause or exacerbate dry eye.Therefore,the study of changes in the meibomian glands in dry eyes is important for understanding the pathogenesis of dry eyes in depth and finding new targets for the treatment and prevention of dry eyes. OBJECTIVE:To investigate the changes of the meibomian gland in a mouse model of aqueous deficient dry eyes. METHODS:Thirty-two female C57/B6 mice at 6-8 weeks were selected and randomly divided into experimental and control groups with 16 mice in each group.The mice in the experimental group were constructed by removing both the extra-orbital and intra-orbital lacrimal glands,while those in the control group were not treated.After 2 weeks of normal feeding,the corneal changes of both groups were observed under a slit lamp,and the tear secretion of both groups was measured.The meibomian glands of the two groups of mice were removed after decapitation.The changes in the gross morphology of the meibomian glands were observed and the meibomian glands were made into frozen sections.Hematoxylin-eosin staining was used to observe the structure of the meibomian glands,oil red staining was used to evaluate the function of the meibomian glands,and immunofluorescence staining and RT-qPCR were used to observe the expression of cytokeratin 14,Ki67 and abnormally differentiated small proline-rich protein 1B in the meibomian glands of mice. RESULTS AND CONCLUSION:Two weeks after modeling,lamellar defects were seen in the corneas of the experimental mice,and neovascularization of the limbal corneal was generated and invaded the central cornea.(2)Tear secretion volume was significantly reduced in the experimental group compared with the control group(P<0.05).Microscopic findings showed that the ducts of the meibomian glands in the experimental group were interrupted and atrophied,and their arrangement was disorganized.Hematoxylin-eosin staining results showed a significant increase in lipid vacuoles in the meibomian glands of the experimental mice compared with the control group.Lipid deposition was seen in oil red staining in the experimental group.Immunofluorescence and RT-qPCR results showed a significant increase in the expression of cytokeratin 14,Ki67 and small proline-rich protein 1B in the meibomian glands of mice in the experimental group compared with the control group(P<0.05).To conclude,aqueous deficient dry eye can lead to compensatory hypertrophy,increased proliferation,and abnormal lipid metabolism in the meibomian gland,as well as abnormal differentiation of the meibomian gland.

Research status of correlation between myopia and accommodative function / 国际眼科杂志(Guoji Yanke Zazhi)

Ocular accommodation refers to the process by which the ciliary muscle creates a clear image of the object in the retina by changing the refractive power of the lens. When the accommodation ability of the eye is insufficient, the imaging focus falls on the region behind the retina and hyperopic defocus is easily formed, resulting in axial growth and leading to the development of myopia, and it is found that most myopic patients usually have some accommodation dysfunction. Myopia has become a public health problem in China, and the prevalence of adolescents has increased dramatically. How to prevent and stop the occurrence and development of myopia is a major challenge. Previous studies have found that ocular accommodation dysfunction is associated with the occurrence and development of myopia, and the measurement of parameters related to accommodation function has certain guiding significance for the prevention and control of myopia. The purpose of this paper is to review the correlation between myopia and ocular accommodation function, with a view to providing new ideas for the prevention, control and treatment of myopia.

Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans / 中华外科杂志

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

Analysis of the characteristics of primary acute myeloid leukemia with 11q23/KMT2A rearrangements in ninety patients / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements.@*METHODS@#Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively.@*RESULTS@#By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT.@*CONCLUSION@#The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.

Determination of chemical component and quality control evaluation of Paeoniae Radix Alba / 国际中医中药杂志

Objective:To establish a method for the determination of four effective components in Paeoniae Radix Alba and evaluate its quality of Paeoniae Radix Alba by principal component analysis. Methods:The effective components of Paeoniae Radix Alba were extracted by ultrasonic extraction method with ethanol. Wondasil WR C18 chromatographic column (250 mm×4.6 mm,5 μm) was used, and the mobile phase was acetonitrile-water, the flow rate was set at 1 ml/min, the column temperature was set at 30 ℃, and the total operation time was 65 min. The mass score of active components was imported into SPSS for principal component analysis. Results:The linear ranges of Paeoniflorin, Paeoniflorin, Benzoyl Paeoniflorin and Pallyl Paeoniflorin were 0.020 1-3.820 0 μg ( r2=0.999 4), 0.015 9-2.850 0 μg ( r2=0.999 2), 0.008 2- 1.820 0 μg ( r2=0.999 1), 0.003 2-0.970 0 μg ( r2=0.999 5). The quality of the 10 batches of Paeoniae Radix Alba samples from Anhui province was the best, while that from Sichuan province was the worst. Conclusions:HPLC method was established for the determination of four effective components in Paeoniae Radix Alba, and principal component analysis and evaluation of 10 batches of Paeoniae Radix Alba. Bozhou, Anhui Province, was identified as the main production area of Paeoniae Radix Alba, which can provide reference for the quality control and preparation production of Paeoniae Radix Alba.

Serum alpha-fetoprotein in predicting survival of patients with BCLC C hepatocellular carcinoma treated by salvage surgery after downstaging therapy / 中华肝胆外科杂志

Objective:To analyze the value of alpha-fetoprotein(AFP) in predicting survival of patients who underwent salvage surgery after tumor downstaging therapy in patients with advanced hepatocellular carcinoma.Methods:The data of 50 patients with Barcelona Clinic Liver Cancer Staging (BCLC) C hepatocellular carcinoma treated at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from December 2018 to December 2021 were collected. There were 45 males and 5 females, with the age of (53.0±10.5) years. The patients were divided into two groups based on the serum AFP level after tumor downstaging therapy, AFP normal group ( n=27, AFP≤20 μg/L) and the control group ( n=23, AFP>20 μg/L). Patient survival and tumor recurrence were followed up by outpatient review or telephone follow-up. The survival rate was calculated by the Kaplan-Meier method and compared by the log-rank test. The efficacy of combined immunotargeted therapy were compared between the two groups. Univariate and multivariate Cox regression analysis were carried to analyse the factors influcing prognosis. Results:The median survival time was not reached in both groups. The 1-year and 2-year cumulative survival rates were 95.0% and 88.2% in the normal group and 73.4% and 54.1% in the control group, respectively. The median relapse-free survival time of the normal group was not reached, and the median relapse-free survival time of the control group was 11 months. The 1-year recurrence-free survival rate was 78.1% in the normal group and 39.5% in the control group. The cumulative survival rate and relapse-free survival rate in the normal group were significantly higher than those in the control group (χ 2=7.60, 8.83, P=0.006, 0.003). The complete response, partial response and pathological complete response of tumors in the normal group were significant better than those in the control group. Multivariate Cox regression analysis showed that patients with serum AFP >20 μg/L ( HR=2.952, 95% CI: 1.023-8.517, P=0.045) after immunotherapy combined with targeted therapy had an increased risk of postoperative recurrence. Conclusion:The reduction of serum AFP to normal after downstaging therapy could be used as a prognostic indicator of salvage surgical in patients with BCLC C hepatocellular carcinoma, and AFP was related to the efficacy of downstaging therapy in patients.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study / 대한뇌졸중학회지

Background@#and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. @*Methods@#In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). @*Results@#Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. @*Conclusion@#This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Effect of High-Concentration Uric Acid on Nitric Oxide / 中国医学科学院学报

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.

Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart / 医学前沿

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.

Efficacy of postmastectomy radiotherapy for HER2-positive T 1-2N 1M 0 breast cancer / 中华放射医学与防护杂志

Objective:To investigate the efficacy of postmastectomy radiotherapy (PMRT) for human epidermal growth factor receptor 2 (HER2)-positive T 1-2N 1M 0 breast cancer in the context of HER2-targeted therapy. Methods:This study collected the clinical data of 105 female patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy in the First Affiliated Hospital of Bengbu Medical College from January 2013 to December 2019. Then, the clinical outcomes of these patients were observed, and the prognostic factors and the efficacy of PMRT were analyzed. Results:The median follow-up time was 50 months (ranging from 14 to 107 months), and the 5-year overall survival (OS), local-regional recurrence-free survival(LRFS), and disease-free survival (DFS) were 81.6%, 91.9%, and 76.2%, respectively. The multivariate analysis indicated that independent prognostic factors for OS and DFS include the age, pathologic grade, and tumor size; the independent risk factors for LRFS include positive lymph node ratio (LNR) and hormone receptor (HR) status; and the independent prognostic factor for DFS was PMRT (HR: 2.85, 95% CI: 1.10-8.80, P < 0.05). The subgroup analysis suggested that PMRT significantly improved the OS of various high-risk subgroups ( χ2=4.01-9.18, P < 0.05). However, the further stratified analysis indicated that PMRT only increased the OS of the patients who did not receive HER2-targeted therapy in various high-risk subgroups ( χ2=4.50-6.70, P < 0.05), while there was no statistical difference before and after PMRT for the individuals who received targeted treatment ( P > 0.05). Conclusions:PMRT is an independent prognostic factor for the DFS of patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy. PMRT can improve the OS of high-risk patients with ages < 45 years old, pathologic grade Ⅲ, tumor diameter ≥ 3 cm, LNR > 10%, and HR (-) who received no HER2-targeted therapy. However, the efficacy may be compromised to some extent in the context of the application of HER2-targeted therapy.

Effects of the deep inspiration breath-hold technique on cardiac dosimetry in internal mammary node irradiation with intensity-modulated radiation therapy for postoperative left breast cancer / 中华放射医学与防护杂志

Objective:To explore the effects of the deep inspiration breath-hold (DIBH) technique on cardiac dosimetry in internal mammary node irradiation with intensity-modulated radiation therapy (IMN-IMRT) for postoperative left breast cancer.Methods:Totally 23 left breast cancer patients in the First Affiliated Hospital of Bengbu Medical College from Octorber 2021 to July 2022 receiving postoperative IMN-IMRT were enrolled in this study. The changes in dosimetric parameters for their heart and left anterior descending coronary artery (LAD) in the DIBH mode were observed, and the potential factors affecting DIBH effects were analyzed.Results:Compared with the free breath (FB) mode, the DIBH mode manifested a heart volume decrease by 18% ( t = 10.47, P < 0.001), a left lung volume increase by 42% ( t = -14.55, P < 0.001), and significantly reduced dosimetric parameters ( Dmean, Dmax, V5- V30) for the heart and LAD, exhibiting statistically significant differences ( t=-13.38 to -3.30, P<0.05). As indicated by the Pearson correlation analysis, the relative ratio of cardiac dose reduction was positively correlated with that of left lung expansion ( r = 0.82, P < 0.001) and negatively correlated with the patient′age ( r = -0.56, P = 0.005). Conclusions:DIBH can effectively reduce the heart and LAD radiation doses in IMN-IMRT for postoperative left breast cancer and that the patient's age, and the DIBH effects might be affected by the vital capacity.

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

Construction and validation of nomograms for predicting the prognosis of late-stage hepatocellular carcinoma / 国际外科学杂志

Objective:To construct and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) of patients with late-stage hepatocellular carcinoma (HCC).Methods:A retrospective cohort study was used in this report. Screened 2382 late-stage HCC patients obtained from Surveillance, Epidemiology, and End Results (SEER) database (2010—2015), were randomly classified into the training cohort and the internal validation cohort by using the function in R software according to the ratio of 1∶1. Chi-square test was applied to verify the comparability of data between two groups. The external validation cohort ( n=62) were collected from the Affiliated Zhangjiagang Hospital of Soochow University. Based on univariate and multivariate COX regression analyses in the training cohort, this study constructed nomograms for 6- and 12- month OS and CSS. Concordance index (C-index), calibration plots, the receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were applied to measure the performance of nomograms in the training cohort and to validate nomograms in two validation cohorts. The clinical utility was measured by decision curve analysis (DCA). Results:Two nomograms were constructed. The identified risk factors included sex, Edmondson-Steiner grade, T stage, N stage, M stage, tumor size, bone metastasis, Alpha-fetoprotein (AFP), surgery of primary site, radiation and chemotherapy. The C-index for OS in the training and two validation cohorts was 0.729(95% CI: 0.711-0.747), 0.721(95% CI: 0.705-0.737) and 0.860(95 CI: 0.831-0.889), respectively. The C-index for CSS in the training and two validation cohorts was 0.732(95% CI: 0.714-0.750), 0.725(95% CI: 0.707-0.743) and 0.862(95% CI: 0.829-0.895), respectively. Afterwards, for nomograms in the training and two validation cohorts, C-index and calibration plots expressed great predictive accuracy and concordance. ROC curves and Kaplan-Meier survival curves demonstrated good prognostic ability. Furthermore, nomograms performed superior to other models. DCA showed substantial clinical utility. Conclusion:This study has developed and validated nomograms predicting 6- and 12- month OS and CSS of patients with late-stage HCC, which may be useful to develop the individualized treatment.

Expression change and clinical significance of plasma miR-128-3p in patients with severe pancreatitis / 中华内分泌外科杂志

Objective:To detect the expression and clinical significance of microRNA-128-3p (miR-128-3p) in the plasma of patients with severe pancreatitis (SAP) .Methods:A total of 175 patients with acute pancreatitis who were treated in our hospital from Jun. 2017 to Dec. 2020 were selected as observation objects. According to the severity of the patients, the patients were divided into 78 cases in mild acute pancreatitis (MAP) group, 50 cases in moderate to severe acute pancreatitis (MSAP) group and 47 cases in severe acute pancreatitis (SAP) group; according to the patient’s prognosis, the SAP group was divided into 28 cases in the survival group and 19 cases in the death group. The level of miR-128-3p was detected by qRT-PCR method, and patients were evaluated with Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score and Ranson score, the correlation between plasma miR-128-3p level and APACHEⅡ, Ranson score was analyzed by Pearson, the predictive value of plasma miR-128-3p for poor prognosis of SAP patients was analyzed by ROC curve.Results:There were statistically significant differences in APACHE II[ (3.41±1.56) , (5.63±1.78) , (6.57±1.83) points], Ranson [ (2.58±1.34) , (4.95±1.47) , (6.06±1.92) points] and plasma CRP [ (39.73) ±12.31) , (70.25± 24.38) , (142.51±40.55) mg/L], serum calcium [ (1.95±0.31) , (13.26±5.24) , (14.21±6.32) mmol/L], among the MAP group, MSAP group and SAP group ( P<0.05) ; Compared with the MAP group (1.05±0.12) , the plasma miR-128-3p expression levels in the MSAP group (0.83±0.08) and the SAP group (0.57±0.05) were significantly decreased ( P<0.05) ; compared with the MSAP group (0.83±0.08) Compared with the SAP group (0.57±0.05) , the plasma miR-128-3p expression level was significantly decreased ( P<0.05) ; Compared with the survival group [ (0.65±0.08) , (5.91±1.64) points, (5.45±1.25) points, (120.43±30.56) mg/L], the plasma miR-128-3p of SAP patients in the death group was (0.43±0.05) expression levels were significantly reduced, APACHE II [ (7.43±2.21) points], Ranson score [ (7.22±1.59) points] and plasma CRP level [ (171.52±42.38) mg/L] were significantly increased ( P<0.05) ; the results of correlation analysis showed that plasma miR-128-3p level was negatively correlated with APACHEⅡ and Ranson scores ( r=-0.531, -0.609, P<0.05) ; The diagnostic efficacy of plasma miR-128-3p in predicting poor prognosis of SAP patients is better than APACHEⅡ, Ranson score, and CRP. Conclusion:Plasma miR-128-3p level is elevated in patients with severe pancreatitis, which is of certain value for the diagnosis and prognostic evaluation of SAP.

Evolution and Connotations of "Prohibition"， "Contraindication"， or "Use with Caution" in Chinese Materia Medica / 中国实验方剂学杂志

This study systematically combed and analyzed the use of such terms as "prohibition"， "contraindication"， and "use with caution" in ancient Chinese books on materia medica and prescriptions， Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， and teaching materials and monographs of Chinese materia medica by means of hermeneutics， commentariology， textology， and data mining， and explored the historical evolution and conceptual connotations of "prohibition"， "contraindication"， and "use with caution" in Chinese materia medica， so as to provide reference for standardizing their understandings and clinical reasonable medication. The "prohibition"， "contraindication"， and "use with caution" of Chinese materia medica were first proposed in the period of pre-Qin and Han dynasties. "Prohibition" and "contraindication" were separately developed in the Sui， Tang， and Five dynasties and Song， Jin， and Yuan dynasties and have been widely used since the Ming and Qing dynasties. The "use with caution" becomes popular rapidly in modern times and is often present in clinical medication together with "prohibition" and "contraindication". "Prohibition" basically means strictly prohibited and "contraindication" means to avoid as much as possible. The terms "prohibition"， "contraindication"， and "use with caution" have experienced evolution from the pre-Qin period to modern times， and they are used to describe the degree of restriction on drug use（"prohibition" > " contraindication" > "use with caution"）.

Ionizing radiation promotes epithelial-mesenchymal transition of cervical cancer cell line Siha through increasing the secretion of exosomes / 中华放射医学与防护杂志

Objective:To observe the occurrence of epithelial-mesenchymal transition (EMT) in cervical cancer cell line Siha irradiated by X-rays with clinical conventional fraction radiotherapy model and investigate the role of exosomes in this process.Methods:Siha cells were irradiated by 6 MV-X rays with 50 Gy in 25 fractions. EMT was evaluated by cell morphology, EMT biomarkers and cell migration and invasion ability. Exosomes released from cells were detected by transmission electron microscopy and nanoparticle tracking analysis (NTA), and its function in EMT was explored by using an exosome inhibitor GW4869 (10 μmol/L).Results:After irradiation, EMT phenomenon was induced in the survived Siha cells, including the incidence of mesenchymal phenotype, upregulation of epithelial marker E-cadherin ( t=9.66, P<0.05), downregulation of mesenchymal marker N-cadherin ( t=41.61, P<0.05), and increase of cell migration and invasion abilities ( t=6.11, 13.22; P<0.05). Meanwhile, the secretion of exosomes was also increased after irradiation ( t=7.51, P<0.05). When the cells were pre-treated with GW4869, radiation-induced exosome secretion was reduced ( t=7.28, P<0.05), so that radiation-induced EMT was reversed. Conclusions:Ionizing radiation with clinical conventional fraction radiotherapy model promotes EMT of cervical cancer cells through increasing the secretion of exosomes.

Effects of knocking down TSPO on proliferation and autophagy of BV2 cells in OGD/R models / 中国药理学通报

Aim To investigate the effeets of prolifera¬tion and autophagy of BV2 eells in OGD/R models when the 18 ku transloeator protein( TSPO) was inhibi¬ted.Methods BV2 microglia were eultured in vitro and the model established by oxygen-glueose depriva- tion/reperfusion( OGD/R) , the eells were divided into eontrol group and OGD/R group, OGD/R + small hair¬pin RNA negative eontrol group ( OGD/R + NCshR- NA) , OGD/R + TSPO small hairpin RNA group (OGD/R + TSPOshRNA ).The expression of TSPO mRNA and TSPO protein were deteeted by qRT-PCR and Western blot, respectively.In order to study the effeet of TSPO on BV2 microglial eells in OGD/R inju¬ry and autophagy, the cell viability was tested by CCK- 8 assey, the cytotoxicity was deteeted by reactive oxy¬gen speeies ( ROS) , autophagy-related mRNA ( p62 mRNA, LC3B mRNA, Beolin-1 mRNA) expressions were detected by qRT-PCR, and the expression levels of autophagy -related proteins ( p62 , LC3 II /LC3 1 , Beclin-1 ) were detected by Western blot in each group.Result The expression of TSPO mRNA and protein increased significantly in OGD/R group while compared to control group, the cell death and cytotox¬icity increased significantly, the expression levels of LC3B mRNA and Beclin-1 mRNA increased, while the p62 mRNA decreased significantly, the levels of LC3 II/LC3 1 and Beclin-1 protein increased, the expres¬sion of p62 protein decreased significantly in OGD/R group, and the autophagy was activated; compared with OGD/R group, the different levels of cell viabili¬ty, cytotoxicity and autophagy in OGD/R + NCshRNA group were not statistically significant.But the survival rate of cells in OGD/R + TSPOshRNA group signifi¬cantly increased, the levels of cytotoxicity and autoph¬agy were significantly reduced.Conclusions The in¬hibition of TSPO has a significant protective effect on OGD/R injury model in BV2 microglial cells, which may be related to the inhibition of autophagy.

Effect of Wnt5b overexpression on the differentiation of embryonic liver stem cells in mice and its repair effect on chronic liver injury in mice / 解剖学报

[Abstract] Objective To investigate the effect of wingless-type MMTV integration site family member 5b(Wnt5b) gene overexpression mediated by recombinant adenovirus on the differentiation of mouse embryonic liver stem cells and repair of chronic liver injury in mice. Methods Recombinant adenoviruses expressing Wnt5b and green fluorescent protein (GFP) were applied respectively to infect mouse fetal liver stem cells HP14-19, and induced its differentiation and verified the expression of Wnt5b through Real-time PCR and Western blotting. It also applied indocyanine grean(ICG) uptake experiment and periodic acid-schiff(PAS) staining to detect the differentiation ability of HP14-19 into hepatocyte-like cells. The Real-time PCR was chosen to detect hepatocyte markers albumin (Alb) and cytokeratin 18 (CK18) expression. Forty-eight experimental male BALB/ c mice were randomly divided into control group, model group, stem cell treatment group and Wnt5b modified stem cell treatment group. The carbon tetrachloride(CCl