Myopia shows a trend of high incidence and low age,and the number of high myopia patients is increasing year by year.Safe and effective myopia intervention measures are the top priority of myopia prevention and control.It has been found that low-dose atropine,orthokeratology,repeated low-level red light and other treatment methods have reliable efficacy,which can provide a variety of options for myopia prevention and control in children.The choroid,as an impor-tant anatomical structure of the fundus,is closely related to the mechanism of myopia.Choroidal parameters may become markers for evaluating the effect of myopia prevention and control and monitoring the progression of myopia.With the con-tinuous development of medical imaging technology,choroidal thickness and microcirculatory parameters have been accu-rately quantified.Further exploration of the changes of choroid under various myopia intervention measures will help clini-cians design personalized treatment plans for different patients,which is of great clinical significance for the management of myopia prevention and control.In this article,the research progress on choroidal thickness and blood flow changes under different myopia prevention and control measures are reviewed.

Objective:To compare the therapeutic effects of 0.05% cyclosporine and 0.1% fluorometholone eye drops in patients with moderate and severe dry eye.Methods:A randomized controlled study was conducted.Fifty-two patients (52 eyes) with moderate to severe dry eye in Tianjin Medical University Eye Hospital from August 2021 to December 2022 were enrolled and randomly divided into 0.05% cyclosporine group and 0.1% fluorometholone group by random number table method, with 26 cases (26 eyes) in each group.Patients received 0.05% cyclosporine eye drops (2 times/day) and 0.1% fluorometholone eye drops (2 times/day) combined with calf blood deproteinized extract eye drops (4 times/day) according to the grouping.Before and 1, 3 and 6 months after treatment, clinical symptoms and signs were observed and Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS) score, Schirmer Ⅰ test (SⅠT), non-invasive first tear film break-up time (NIBUTf), and conjunctival goblet cell (CGC) density were recorded.Before treatment and after 6 months of treatment, changes in corneal nerves and dendritic cells (DC) were observed by in vivo confocal microscopy (IVCM).This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Eye Hospital of Tianjin Medical University (No.2021KY-17).Written informed consent was obtained from each subject. Results:Compared with the 0.1% fluorometholone group, CFS score decreased after 1 month of treatment, but SⅠT, NIBUTf and CFS score increased after 3 months of treatment, and OSDI score, SⅠT and CFS score decreased after 6 months of treatment in the 0.05% cyclosporine group, showing statistically significant differences (all at P<0.05).Compared with baseline, in the 0.05% cyclosporine group, NIBUTf increased and CFS score decreased after 1 month of treatment, OSDI score and CFS score decreased, SⅠT and NIBUTf increased after 3 and 6 months of treatment, showing statistically significant differences (all at P<0.05).In the 0.1% fluorometholone group, CFS score decreased after 3 months of treatment, OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to baseline, showing statistically significant differences (all at P<0.05).OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to 3 months of treatment in the 0.05% cyclosporine group, and the differences were statistically significant (all at P<0.05).Baseline and CGC densities after 1, 3 and 6 months of treatment were (147.66±17.29), (195.44±15.46), (210.36±19.15) and (282.09±22.63)cells/mm 2 in the 0.05% cyclosporine group and (138.09±17.29), (95.67±15.46), (117.77±19.15) and (109.13±22.63)cells/mm 2 in the 0.1% fluorometholone group, respectively, with a statistically significant overall difference ( Fgroup=11.724, P<0.001; Ftime=4.837, P=0.005).Compared with the 0.1% fluorometholone group, CGC density in the 0.05% cyclosporine group increased after 1, 3 and 6 months of treatment, with statistically significant differences (all at P<0.05).Compared with baseline, the CGC density increased in the 0.05% cyclosporine group after 1, 3 and 6 months of treatment, and the differences were statistically significant (all at P<0.05).Compared with the 0.1% fluorometholone group, the corneal nerve fiber density in the 0.05% cyclosporine group increased after 6 months of treatment, and corneal DC density, area and dendrite number decreased, showing statistically significant differences (all at P<0.05). Conclusions:Cyclosporine 0.05% eye drops combined with calf blood deproteinized extract eye drops can improve symptoms and signs in patients with moderate to severe dry eye, and the long-term effect is better than that of 0.1% fluorometholone plus calf blood deproteinized extract eye drops.

Objective:To investigate the effect of interferon, interleukin 2 (IL-2) combined with lenalidomide in the treatment of acute myeloid leukemia (AML) with minimal residual disease (MRD)-positive.Methods:The clinical data of 1 elderly AML patient with persistent MRD positive treated with interferon, IL-2 combined with lenalidomide in the Affiliated Cancer Hospital of Zhengzhou University in December 2019 were retrospectively analyzed, and the relevant literature was reviewed.Results:The 72-year-old male patient was diagnosed as AML-M 2b with c-kit mutation, the low-risk group according to laboratory related examinations, flow cytometry, genetic testing. The patient did not achieve remission after 1 cycle of standard VA (venetoclax + azacitidine) regimen, and achieved complete remission (CR) after another 1 cycle of IA (idarubicin + cytarabine) induction regimen, followed by consolidation therapy with medium dosage cytarabine and D-CAG (decitabine + cytarabine + aclarubicin + granulocyte colony-stimulating factor) regimen, during which the AML1-ETO fusion gene progressively increased. After programmed death receptor 1 (PD-1) inhibitor-based combination therapy, the AML1-ETO fusion gene remained negative for more than 1 month, and then increased again; subsequently, the patient was treated with the ITI (interferon, thalidomide, and interleukin-2) regimen, and the AML1-ETO fusion gene remained negative for more than 7 months; thalidomide was changed to lenalidomide after the increase again, and AML1-ETO fusion gene remained negative again for 2 years until May 2023. Conclusions:Interferon, IL-2 combined with lenalidomide have a significant therapeutic efficacy in reversing MRD positive and have mild adverse reactions, which can be used as a new option for refractory AML.

Scutellaria baicalensis Georgi, one of the commonly used Chinese herbal medicines in clinic, has a variety of chemical components, mainly flavonoids, including baicalein, baicalin, wogonin. And its pharmacological effects include anti-tumor, antibacterial, antiviral, and antioxidant. The bone marrow microenvironment is a complex network structure composed of mesenchymal stem cells, hematopoietic stem cells, extracellular matrix and various soluble factors. Its malignant transformation affects the development and progression of hematological diseases such as leukemia. Studies have found that scutellaria baicalensis Georgi can act on various components of the bone marrow microenvironment. By influencing related signal transduction pathways, cytokines, apoptosis pathways and energy metabolism pathways, the development and progression of leukemia and multidrug resistance are regulated. This review summarizes the correlation of scutellaria baicalensis and its main compounds with leukemia, explores the potential options of leukemia treatment, so as to provide ideas of seeking new targets of leukemia and related regulatory pathways.

Objective:To investigate the expression of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in patients with acute myeloid leukemia (AML) and its relationship with clinical features and prognosis, and to examine its effect on PD-1-positive natural killer (NK) cells against AML cells in vitro.Methods:The bone marrow samples of 65 AML patients and the peripheral blood of 32 AML patients diagnosed in Affiliated Cancer Hospital of Zhengzhou University from July 2019 to December 2020 were prospectively collected, and the peripheral blood of 24 healthy people was taken as healthy control. The expression level of PD-L1 in bone marrow tumor cells and expression level of PD-1 in peripheral blood NK cells were detected by flow cytometry. The correlations of PD-1 expression in bone marrow tumor cells and PD-1 expression in NK cells with the clinicopathological features, curative effect and prognosis of patients were analyzed. Flow cytometry was used to detect the expression level of PD-L1 in AML cell line THP-1 (target cells) and the expression level of PD-L1 in NK cell line NKL (effector cells). THP-1 cells treated with and without 25 μmol/L of PD-L1 inhibitor fraxinellone were used as experimental group and control group, and co-cultured with NKL cells at different effector-to-target ratios. The apoptosis of THP-1 cells and the expression of NKG2D in NKL cells were detected by flow cytometry, the cell proliferation status was detected by CCK-8 and the cell proliferation inhibition rate was calculated; the levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of co-culture system were detected by enzyme-linked immunosorbent assay (ELISA).Results:The proportion of AML patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in the healthy control group [38.5% (25/65) vs. 8.3% (2/24), P = 0.029]. The proportion of AML patients with PD-1-positive expression in peripheral blood NK cells was higher than that in the healthy control group [40.6% (13/32) vs. 12.5% (3/24), P = 0.035]. There were no statistical differences in sex, age, hemogram, proportion of primordial cells, risk stratification, chromosomal karyotype, gene mutation (except NPM1 gene), fusion gene and French-American-British cooperative group (FAB) typing between patients with PD-L1 positive and negative in bone marrow tumor cells and between patients with PD-1 positive and negative in peripheral blood NK cells (all P > 0.05). In relapsed/refractory patients, the proportion of patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in newly treated patients [58.8% (10/17) vs. 31.2% (15/48), P = 0.045]. There was no significant difference in the proportion of patients with PD-1-positive expression in peripheral blood NK cells between relapsed/refractory patients and newly treated patients [(38.5% (5/13) vs. 42.1% (8/19), P = 0.837]. There was no statistical difference in complete remission (CR) rate between PD-L1 positive and negative patients [69.6% (16/23) vs. 74.3% (26/35), P > 0.05]. There was no statistical difference in CR rate between PD-1 positive and negative patients [66.7% (8/12) vs. 70.6% (12/17), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-L1 positive and negative patients [12.5% (2/16) vs. 19.2% (5/26), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-1 positive and negative patients [25.0% (2/8) vs. 16.7% (2/12), P > 0.05]. Flow cytometry showed that the positive rate of PD-1 in NKL cells was (67±6)% and the positive rate of PD-L1 in THP-1 cells was (85±5)%. After co-culture with NKL cells, the apoptotic rate and proliferation inhibition rate of THP-1 cells were higher in the experimental group compared with the control group, the expression of NKG2D on the surface of NKL cells was elevated, and the levels of IFN-γ and TNF-α in the co-culture supernatant were increased. Conclusions:In AML patients, the expression of PD-L1 in bone marrow tumor cells is high, and the expression of PD-1 in peripheral blood NK cells is also high. The expression of PD-L1 in bone marrow tumor cells of relapsed/refractory AML patients is higher than that of newly treated patients. Inhibition of PD-L1 expression in THP-1 cells can enhance the tumor killing activity of NKL cells in vitro. The mechanism may be that inhibition of PD-L1 expression in THP-1 cells up-regulates the expression of NKL cell activated receptor NKG2D and promotes the secretion of IFN- γ and TNF- α.

Objective:To observe the prevention and control effect of 1% atropine on the progression of form deprivation myopia (FDM) in guinea pigs and the potential biological mechanism.Methods:Sixty-nine 3-week-old tricolor guinea pigs with normal refraction were randomly divided into a normal control group ( n=19), a FDM group ( n=19), a FDM+ atropine group ( n=19), and an atropine group ( n=12). No intervention was given to guinea pigs in normal control group.The FDM model was established by covering the right eye of guinea pigs with a semitransparent latex facemask for 4 weeks in FDM and FDM+ atropine groups.For the FDM+ atropine group, 1% atropine gel was topically administered to the form-deprived right eyes once a day for 4 weeks.For the atropine group, the right eye was treated with 1% atropine gel once a day for 4 weeks.Refraction and axial length of guinea pigs were measured by retinoscopy and ophthalmic A-scan ultrasonography respectively at baseline, experiment week 2 and week 4.In experiment week 4, eyeballs were enucleated to make sections via the paraffin wax processing procedure, and the microstructural and ultrastructural changes of the sclera were observed under the light microscope and transmission electron microscope, respectively.The isobaric tags for relative and absolute quantitation labeling combined with liquid chromatography-tandem mass spectrometry were used to identify the differentially expressed proteins.Use and care of the animals complied with the Regulation for the Administration of Affairs Concerning Experiment Animals by State Science and Technology Commission.The study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.TJYY2020111028). Results:There were statistically significant differences in the diopter of guinea pigs at different time points among the four groups ( Fgroup=138.892, P<0.001; Ftime=167.270, P<0.001). Compared with normal control group, the diopter of guinea pigs in FDM group at experiment weeks 2 and 4, and FDM+ atropine group at experiment week 4 developed toward myopia, showing statistically significant differences (all at P<0.001). Compared with FDM group, the diopter of guinea pigs in FDM+ atropine group at experiment weeks 2 and 4 developed toward hyperopia, showing statistically significant differences (both at P<0.001). There were statistically significant differences in the axial length of guinea pigs at different time points among the four groups ( Fgroup=32.346, P<0.001; Ftime=353.797, P<0.001). The axial lengths of FDM group at experiment weeks 2 and 4 and FDM+ atropine group at experiment week 4 were longer than those of normal control group, and the axial lengths in FDM+ atropine group at experiment weeks 2 and 4 were shorter than those in FDM group, and the differences were statistically significant (all at P<0.001). The collagenous fibers of posterior sclera of guinea pigs were loose and disordered in FDM group, and were regular in FDM+ atropine group.The posterior scleral thickness of normal control group, FDM group, FDM+ atropine group and atropine group was (141.74±16.98), (101.46±9.15), (112.74±6.24) and (134.30±18.19) μm, respectively, with a statistically significant difference ( F=6.709, P=0.005). The posterior sclera was significantly thinner in FDM group than in normal control group and FDM+ atropine group (both at P<0.05). The diameter of posterior scleral collagen fiber gradually increased from inside to outside in normal control group, FDM+ atropine group and atropine group, and the diameters of the inner, middle and outer posterior scleral collagen fibers were smaller in FDM group than in normal control group.Proteomic analysis revealed 85 differentially expressed proteins (fold change>1.30) between FDM group and normal control group, FDM+ atropine group and FDM group, of which 38 were up-regulated and 47 were down-regulated after atropine treatment.Gene Ontology enrichment analysis showed that biological processes mainly involved were biological regulation, cell process, localization and metabolic process.Molecular function mainly involved were binding, catalytic activity, molecular function regulator, structural molecule activity and transporter activity.Cell components mainly involved were in cellular anatomical entity, intracellular and protein-containing complex. Conclusions:Atropine can increase the diameter of scleral collagen fibers in guinea pigs of FDM model, improve the arrangement of scleral collagen fiber, inhibit scleral thinning.The mechanism of atropine to control myopia progression is closely related to the tight junction between scleral cells, cytoskeleton and extracellular matrix remodeling.

Objective:To evaluate the effect of short-term topical administration of atropine eye drops with various concentrations and frequencies on eye safety in children.Methods:A double-blind randomized controlled trial was conducted.Sevevty-two children with ametropia or pre-myopia (72 eyes) were enrolled in Tianjin Medical University Eye Hospital from December 2020 to January 2022.The subjects were randomly divided into 0.01% atropine group, 0.02% atropine group and 0.04% atropine group according to a random number table, with 24 cases (24 eyes) in each group.Automatic refraction with an automatic computer optometry device, subjective refraction with a phoropter, intraocular pressure with a non-contact tonometer, axial length by optical biometrics, the amplitude of accommodation (AMP) by the push-up method, pupil diameter with pupilometer, near visual acuity at 33 cm with a standard logarithmic visual acuity chart, tear evaluation with Keratograph 5M and Ocular Surface Disease Index (OSDI) questionnaire survey were performed among all subjects.One drop of 0.01%, 0.02%, and 0.04% atropine was administrated to the study eye according to grouping, and the pupil diameter was measured every 10 minutes until the pupil did not enlarge three times, then the data after a single treatment of the three groups were recorded.After one-week application of the corresponding concentration of atropine eye drops once at night, the data after one-week treatment were recorded.For the next week, the application frequency of 0.01% and 0.02% atropine groups changed to once daily in the morning and evening, and 0.04% atropine group maintained once at night, then the data after two-week treatment were recorded.Data of the right eyes were analyzed.The changes in pupil diameter, AMP and other eye parameters before and after atropine eye drops of the three groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-51). All subjects and their guardians were fully informed of the method and purpose of this study before entering the cohort.Written informed consent was obtained from guardians.Results:Pupil diameters of 0.01%, 0.02% and 0.04% atropine groups were (5.59±0.48), (5.35±0.76) and (5.65±0.43)mm before treatment respectively, (7.00±0.68), (7.17±0.58) and (8.40±1.71)mm after a single treatment, (6.67±0.62), (6.56±0.65) and (7.60±0.69)mm after one-week treatment, (6.96±0.49), (7.04±0.53) and (7.60±0.36)mm after two-week treatment.There were significant differences in pupil diameter at different time points after treatment among the three groups ( Fgroup=9.430, P<0.001; Ftime=156.620, P<0.001). The AMP of 0.01%, 0.02% and 0.04% atropine groups were (12.94±3.02), (13.25±2.81) and (13.42±2.60)D before treatment respectively, (11.62±2.61), (11.53±2.06) and (9.64±1.93)D after a single treatment, (11.14±2.61), (11.33±2.33) and (8.30±1.18)D after one-week treatment, (9.99±1.81), (8.72±1.25) and (8.76±2.12)D after two-week treatment.There was no significant difference in the AMP among the three groups ( Fgroup=2.800, P=0.063). In the three groups, the AMP at different time points after treatment were significantly lower than that before treatment ( Ftime=61.400, P<0.001). There was no difference in spherical equivalent refraction, intraocular pressure, near visual acuity, axial length, first none-invasive tear break-up time, average none-invasive tear break-up time, tear meniscus height and OSDI score among the three groups ( Fgroup=0.030, 0.630, 1.420, 0.580, 0.140, 0.120, 0.340, 0.142; all at P>0.05). There were significant differences in spherical equivalent refraction, intraocular pressure, first none-invasive tear break-up time, average none-invasive tear break-up time, tear meniscus height and OSDI score at different time points between before and after medication among the three groups ( Ftime=12.560, 4.730, 4.720, 5.220, 3.720; all at P<0.05). Conclusions:Varying pupil dilation and AMP reduction occur after the use of different concentrations of atropine and are more severe at higher concentrations.Increased administration frequency of atropine is associated with more pupil dilation and AMP reduction, but there is no intolerable adverse effect.

Objective:To investigate the medium- and long-term efficacy of peroral endoscopic myotomy (POEM) for esophageal diverticulum and the risk factors for postoperative recurrence.Methods:A retrospective study was conducted on 31 cases of esophageal diverticulum who were treated by POEM in Zhongda Hospital, Southeast University from May 1st 2016 to August 1st 2019. The Eckardt score, the operative success rate, and the recurrence rate after the operation were observed and recorded. Multivariate logistic regression analysis was performed to explore the risk factors for postoperative recurrence.Results:POEM was successfully completed in all 31 patients, who were followed up for 30.6±11.1 months (20-63 months). The Eckardt score before the operation was 8.2±2.4, and was 1.4±0.7, 1.4±1.1, 1.3±1.1, and 1.3±0.9 at 1, 6, 12 and 24 months, respectively after the operation, which significantly decreased at all follow-up time points ( P<0.001). The success rates at 1, 6, 12, and 24 months after the operation were 96.8% (30/31), 90.3% (28/31), 90.3% (28/31) and 90.3% (28/31), respectively. Three patients suffered symptom relapse, with an overall recurrence rate of 9.7% (3/31). Logistic regression analysis showed that the disease duration ( P=0.038, OR=1.041, 95% CI: 1.002-1.080) and preoperative Eckardt score ( P=0.024, OR=2.299, 95% CI: 1.117-4.728) were risk factors for postoperative recurrence of POEM. Conclusion:POEM is safe and effective for esophageal diverticulum. Patients with long disease duration and high preoperative Eckardt score are associated with recurrence.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Corona virus disease 2019 （COVID-19） has led to more than 500 million cases， including 6.19 million deaths. Mutated strains of SARS-CoV-2 （alpha， beta， gamma， delta and omicron） have successively emerged. Currently the omicron variant is gradually replacing the delta variant， driving a surge of cases in most countries including China， posing a great challenge to the prevention and treatment of COVID-19. In the face of the severe pandemic situation， a large number of non-medical volunteers are fighting on the front lines of the war against the pandemic and are vulnerable to exposure due to lack of professional knowledge. This paper introduces the routine skills training of volunteers and emergency response， aiming to provide behavioral guidance for non-medical volunteers in designated isolation facilities.