Pars plana vitrectomy combined with inverted internal limiting membrane flap technique for treating macular hole retinal detachment in high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of pars plana vitrectomy(PPV)combined with inverted internal limiting membrane flap technique in the treatment of macular hole retinal detachment(MHRD)in high myopia.METHODS: A retrospective clinical study was conducted. A total of 63 patients(64 eyes)with high myopia and MHRD who treated at our hospital from October 2017 to October 2021 were selected as research subjects. They were divided into two groups according to different surgery, with 34 cases(35 eyes)who received PPV combined with inverted internal limiting membrane flap technique in group A, and 29 cases(29 eyes)received PPV combined with internal limiting membrane peeling in group B. The patients were followed up for 6mo. The two groups were compared in terms of the hole closure rate, the reduction rate of retinal detachment and best corrected visual acuity(BCVA)before operation and at 1wk, 1, 3 and 6mo after operation, and the postoperative complications were recorded.RESULTS: The hole closure rate within 6mo after operation was significantly higher in group A than in group B(P<0.05), but there was no statistically significant difference in the reduction rate of retinal detachment(P>0.05). The BCVA of the two groups was significantly improved over time after operation(P<0.05). There was no statistically significant difference in BCVA between the two groups before operation and at 1wk, 1, 3 and 6mo after operation(P>0.05). Complications were observed in the two groups, but there was no statistically significant difference in the incidence of complications between the two groups(P<0.05).CONCLUSION: PPV combined with inverted internal limiting membrane flap technique is safe and effective in the treatment of MHRD in high myopia, which can effectively improve the patients' BCVA and the hole closure rate without influence on intraocular pressure.

Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.@*METHODS@#The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.@*RESULTS@#Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.@*CONCLUSION@#The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.

Single Center Analysis of Bloodstream Infection Clinical Characteristics and Prognosis in Patients with Hematological Malignancies in the Tropics / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection.@*METHODS@#The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied.@*RESULTS@#The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies.@*CONCLUSION@#Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.

Clinical Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of 12 Patients with Acute Leukemia in Tropical Area / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of acute leukemia in the tropical area.@*METHODS@#Twelve acute leukemia patients who were underwent allo-HSCT from April 2013 to November 2018 in Hainan Hospital of Chinese PLA General Hospital were selected, including 5 cases of acute lymphoblastic leukemia (ALL) and 7 case of acute myeloid leukemia (AML). Three cases received HLA matched sibling hematopoietic stem cell transplantation, 8 cases received haploidentical hematopoietic stem cell transplantation, 1 cases received partially mismatched unrelated hematopoietic stem cell transplantation. Pretreatment regimen: 9 cases received modified BU/CY+ATG pretreatment regimen, 3 cases received BU/CY pretreatment regimen. Graft-versus-host disease (GVHD) prevention regimen: all patients received cyclosporine A, mycophenolate mofetil combined with short-term methotrexate regimen. The clinical efficacy of allo-HSCT in treatment of acute leukemia in the tropical area was analyzed by detecting hematopoietic reconstitution, GVHD, infection, relapse and survival after transplantation.@*RESULTS@#All the 12 patients achieved granulocyte reconstruction and megakaryocyte reconstruction. The median time of granulocyte reconstruction was 11.5 (6-14) days, and the median time of megakaryocytic reconstruction was 12.5 (10-22) days. Within 100 days after transplantation, the acute GVHD occurved in 8 cases, including 6 cases of Ⅱ-Ⅳ degree acute GVHD and 2 cases of Ⅲ-Ⅳ degree acute GVHD, 11 cases survived more than 100 days after transplantation, and the chronic GVHD occurred in 1 case, which was mildly limited. Pulmonary infection occurred in 7 cases, cytomegaloviremia occurred in 6 cases, EB viremia occurred in 6 cases, and hemorrhagic cystitis occurred in 5 cases. 2 cases relapsed and eventually died, and the remaining 10 patients survived without disease until the date of follow-up. The median follow-up time was 4 (1-68) months, 83.3% (10/12) survived without disease, and 16.7% (2/12) relapsed.@*CONCLUSION@#Allo-HSCT is an effective method for the treatment of acute leukemia in adults. Leukemia patients should be transplanted as soon as possible after remission. The incidence of pulmonary fungal infection in transplanted patients in tropics is high, therefore the prevention and treatment of fungal infection should be strengthened.

Clinical Characteristics and Prognosis of U2AF1 Mutation in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis.@*METHODS@#A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed.@*RESULTS@#The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01).@*CONCLUSION@#The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.

Profiling and identification of aqueous extract of Cordyceps sinensis by ultra-high performance liquid chromatography tandem quadrupole-orbitrap mass spectrometry / 中国天然药物

Characterization of aqueous extract in traditional Chinese medicine (TCM) is challenging due to the poor retention of the analytes on conventional C columns. This study presents a systematic characterization method based on a rapid chromatographic separation (8 min) on a polar-modified C (Waters Cortecs T3) column of aqueous extract of Cordyceps sinensis. UHPLC-HRMS method was used to profile components in both untargeted and targeted manners by full MS/PIL/dd-MS acquisition approach. The components were identified or tentatively identified by reference standards comparison, fragmentation rules elucidation and available databases search. A total of 91 components, including 10 nucleobases, 20 nucleosides, 39 dipeptides, 18 amino acids and derivatives and 4 other components, were characterized from the aqueous extract of C. sinensis. And this was the first time to systematically report the presence of nucleosides and dipeptides in C. sinensis, especially for modified nucleosides. The chemical basis inquiry of this work would be beneficial to mechanism exploration and quality control of C. sinensis and related products. Meanwhile, this work also provided an effective solution for characterization of aqueous extract in TCM.

Thickness measurement of frequency domain OCT on photoreceptor cell layer in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To compare the outer nuclear layer ( ONL) , inner and outer segments (IS/OS), photoreceptor cell layer in healthy people and diabetic retinopathy by frequency-domain optical coherence tomography ( OCT) .·METHODS: Totally 100 eyes of 50 healthy people were selected as control group. According to conventional mydriasis for examination of fundus and fundus fluorescein angiography ( FFA ) examination, all diabetic cases were divided into 3 groups: normal retina group ( NDR ) , non - proliferative diabetic retinopathy group (NPDR), proliferative diabetic retinopathy group (PDR). Using OCT measure the thickness of ONL, IS/OS and photoreceptor cell layer of fovea and parafovea ( nasal side and temporal side) in the four groups.·RESULTS: Compared with the control group, the ONL and photoreceptor cell layer's thickness of macular fovea and temporal parafovea in NPDR group and PDR group were statistically significant(all P<0. 05). The differences between ONL and photoreceptor cell layer's thickness of macular fovea and temporal parafovea in NDR group and PDR group were not statistically significant(P>0. 05). The IS/OS of macular fovea and temporal parafovea was not significantly different among those groups (P>0. 05). The thickness of different layers of nasal parafovea were not different (P>0. 05).·CONCLUSION: The thickness of macular fovea and temporal parafovea has relation with degree of DR; the change of photoreceptor cell layer's thickness occurs mainly in ONL, but IS/OS no change; the change in temporal parafovea more obvious than in nasal parafovea. Frequency-domain OCT can quantitatively and qualitatively observe the subtle diabetic macular changes in diabetic patients with macular disease, and provides a reliable detection for the early diagnosis and treatment.

Compatibility of hollow hydroxypropyl starch capsules with drug particles of ofloxacin / 中国药学杂志

OBJECTIVE: To investigate the compatibility of hollow hydroxypropyl starch capsules with drug particles of ofloxacin. METHODS: The capsules were placed in conditions of high temperature of 40℃ or high humidity of (75 ± 5)% RH for 5 and 10 d, respectively. The contents and related substances were determined by high performance liquid chromatography (HPLC), and the changes in the drug appearance and colors were observed. RESULTS: After being stored under the conditions of high temperature and high humidity for 5 and 10 d, the contents of ofloxacin were in the range of 90% - 110%, and no new impurities were detected, which conformed to the quality standard of ofloxacin capsules in the Chinese Pharmacopoeia 2010 edition. CONCLUSION: There is good compatibility between ofloxacin and hollow hydroxypropyl starch capsules, which is consistent with the test results of gelatin capsules.

Determination of D(-) sulbenicillin sodium in sulbenicillin sodium for injection by HPLC-MS / 中国药学杂志

OBJECTIVE: To establish a method for determination of D(-) sulbenicillin sodium in sulbenicillin sodium for injection by HPLC/MS. METHODS: The analysis was performed on a SHIMADZU VP-ODS column with mobile phase consisting of 0.01 mol·L-1 ammonium acetate solution-methanol (90:10) at a flow rate of 0.6 mL·min-1. The detection was performed by Multiple Reaction Monitoring (MRM) scanning mode with ESI negative ion mode. RESULTS: D(-) and L(+) sulbenicillin could be effectively separated. Good liner relationship was achieved when the concentration of D(-) sulbenicillin was in the range of 1.03-51.90 μg· mL-1 (r = 0.9997). The average recovery rate was 99.98% at three levels (RSD = 0.30%, n = 9). CONCLUSION: The MRM method is accurate, reliable, and can be used for the determination of D(-) sulbenicillin sodium in sulbenicillin sodium for injection.

Surgical treatment of symptomatic Rathke's cleft cysts: clinical features, therapy considerations and outcomes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rathke's cleft cyst (RCC) is one of the most common incidentally discovered sellar lesions, while symptomatic cases are relatively rare. Surgical treatment is recommended for symptomatic patients to drain the cyst content and to remove the capsule safely. The aim of this study was to clarify the clinical features, surgery considerations and therapy outcomes of symptomatic RCCs.</p><p><b>METHODS</b>Totally 42 patients (19 males and 23 females) were retrospectively reviewed with the diagnosis of RCCs under surgery resection at the Affiliated Hospital of Medical College, Qingdao University between January 2005 and December 2010.</p><p><b>RESULTS</b>Patients' age ranged from 6 to 67 years (mean of 41.6 years). The duration of symptoms ranged from 4 days to 10 years. Headache (69%), visual impairment (36%), and pituitary dysfunction (10%) were the most common presenting symptoms. The maximum diameter of cysts ranged from 6.0 to 46.7 mm (mean of 20.07 mm). Of the 42 patients, 36 underwent endonasal transsphenoidal approach and the others underwent transcranial approach. Thirty patients had a subtotal resection and decompression, while 12 patients had a total cyst resection. Cysts of 28 patients were lined by simple cubical or columnar epithelium, and cysts of 34 patients were filled by amorphous colloid material, that was the characteristic of RCCs. The majority of patients presented with a simple headache, and 93% of this group experienced a complete improvement after surgery. Twelve of 15 patients (80%) with preoperative visual deficits experienced an improvement in their vision after surgery. All of those patients with pituitary dysfunction experienced an improved endocrine status. The endocrinological complication usually was diabetes insipidus, and postoperative transient diabetes insipidus occurred in 13 (31%) patients without any permanent diabetes insipidus. The overall recurrence rate was 7% at a mean follow-up of 22 months (range 12 - 60 months).</p><p><b>CONCLUSIONS</b>Surgical treatment is to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that does not increase the complications. Biopsy and decompression procedures are recommended for most cases.</p>