Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.
Central Nervous System ; Central Nervous System Neoplasms/therapy* ; Critical Illness ; Female ; Humans ; Lymphoma/therapy* ; Male ; Retrospective Studies

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg^-1·d^-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg^-1·d^-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.
Aminobutyrates/pharmacology* ; Animals ; Apelin/metabolism* ; Biphenyl Compounds ; Collagen/metabolism* ; Doxorubicin/pharmacology* ; Fibrosis ; Heart Failure/pathology* ; Male ; Myocytes, Cardiac/pathology* ; RNA, Messenger/metabolism* ; Rats ; Rats, Wistar ; Valsartan/pharmacology* ; Ventricular Function, Left/drug effects* ; Ventricular Remodeling

Objective: To indicate the clinical features of endoscopic transnasal resection of epidural cholesteatoma at paracentral skull base and to analyze its efficacy. Methods: The total excision rate, postoperative complications and postoperative curative effect of 7 patients (4 males and 3 females, aging from 32 to 63 years old) who underwent middle skull base surgery for epidural cholesteatoma resection under transnasal endoscope at Tianjin Huanhu Hospital between August 2017 and August 2020 were retrospectively reviewed. All patients were followed up for 6 to 36 months. The postoperative MRI, clinical symptoms and recurrence were reviewed. Descriptive statistical methods were used for analysis. Results: Among the 7 patients, there were total resection (complete resection of cyst contents and capsule) in 4 patients, near-total resection (complete resection of cyst contents, incomplete resection of cyst capsule) in 1 patient, and subtotal resection (incomplete resection of cyst contents and capsule) in 2 patients. The clinical symptoms of all patients were improved postoperatively with 1 patient who had no clinical symptoms. One case had postoperative cerebrospinal fluid rhinorrhea, which was cured after lumbar drainage and nasal iodoform gauge packing. Up to now, 7 patients (including patients with partial resection) had no recurrence. Conclusion: Endoscopic transnasal approaches may be effectively used for resection of epidural cholesteatoma in the paracentral skull base in carefully selected cases.
Adult ; Cholesteatoma ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Skull Base/surgery*

Angiotensin-Converting Enzyme 2/metabolism* ; COVID-19/virology* ; Disease Susceptibility ; Humans ; SARS-CoV-2/pathogenicity* ; Species Specificity

Objective To analyze the status of knowledge，attitude and practice of the coronavirus disease（COVID ⁃19）among the adults of 18⁃59 years old in China，and to provide scientific basis for corresponding health education strategies. Methods In the rapid development phrase of COVID ⁃ 19，subjects from all provinces or municipalities of China were invited to participate in a quick questionnaire online survey on January 29th，2020. Results The effective response rate of completing questionnaire was 97.41%（3 083/3 165）. 98.54% of the subjects reported that they were very terrified. The main reasons included the high contagion（64.71%）and lack of effective treatments（19.92%）；94.45% of the subjects were concerned that they and their family members would be infected by the novel coronavirus. 99.42% knew that the virus could be transmitted from person to person；97.89% and 93.87% knew that it could spread through respiratory tract and contact respectively，97.73% knew that patients without symptom could also be contagious，96.37% knew that persons in close contact to COVID⁃19 patient were required to be quarantined for at least 14 days of medical observation. 99.09% knew that the pathogen of this disease was novel coronavirus. 65.46% knew that both medical protective masks and surgical masks could prevent COVID⁃19 effectively. 99.68% had confidence in defeating COVID⁃19，and 85.86% believed that COVID⁃19 would be controlled within the next 3 months. Study subjects mainly obtained health information through WeChat（88.97%）or websites（82.06%）. The proportions of the subjects who can cover mouth and nose when coughing or sneezing，avoid hand contacting with eyes，mouth or nose，practice hand hygiene，wear masks outside，avoid exposure to respiratory patients，and avoid the crowded were 89.85%，85.44%，95.13%，96.89%，92.18% and 96.27%，respectively. Multivariate Logistic analysis showed that gender（OR=0.544，95%CI：0.440⁃0.673，P<0.001），age（OR=1.844，95%CI：1.466⁃2.320，P<0.001），recognition （OR=2.200，95% CI：1.780 ⁃ 2.718，P<0.001） were associated with those good behaviors. Conclusion After the happened，the government and society′s vigorous publicity to the public achieved good results. The public are highly concerned and have a high awareness of the knowledge of COVID ⁃ 19. They adopt protective measures proactively. Females，middle⁃aged，and individuals with insufficient recognition are likely under⁃protected. In the different epidemic stages of the emerging infectious disease，health education should be carried out to the public based on scientific evidences.

Objective:To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region.Methods:Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively.Results:511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective β-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment.Conclusion:Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

Objective: To compare the clinical effects of autologous semitendinosus tendon and allogenic tendon arthroscopic anatomical reconstruction of anterior talofibular ligament (ATFL) combined with calcaneofibular ligament (CFL) in the treatment of chronic lateral ankle instability. Methods: A retrospective analysis was made of 55 patients with chronic lateral ankle instability who underwent arthroscopic reconstruction of ATFL combined with CFL from January 2012 to June 2017. A total of 28 cases were treated with autologous semitendinosus tendon (autologous group), including 19 males and 9 females, with an average age of 28.5±8.03 years (range, 16-46 years). A total of 27 cases were treated with allogenic tendon (allogenic group), including 17 males and 10 females, with an average age of 27.48±7.89 years (range, 16-46 years). ATFL/CFL was reconstructed by the same method in both groups. The reconstruction methods were the same between the groups. The talus and calcaneus were fixed with absorbable compression nails. Results: The operation duration in the autologous group was 94.07±7.83 min, which was longer than that in the allogeneic group 63.56±7.96 min (t=14.51, P<0.001). Fever days 5.26±0.90 days in allogeneic group were longer than 2.46±0.74 days in autologous group (t=-12.55, P<0.001). Wound healing duration in allogeneic group was 13.44±3.33 days longer than that in autologous group 10.32±2.34 days (t=-4.01, P<0.001). In the autologous group, 28 cases were followed up for 34.54±16.04 months, and 27 cases in the allograft group were followed up for 42.74±17.79 months. The mean AOFAS score improved from 63.64±11.20 before operation to 90.21±4.48 after operation in the autologous group, and that improved from 63.93±10.59 before operation to 89.56±5.15 after operation in the allogeneic group with no significant difference between the two groups after operation (t=0.506, P=0.615). The mean VAS score decreased from 5.79±1.79 before operation to 1.54±1.35 after operation in the autologous group, and from 5.89±1.78 before operation to 2.04±1.32 after operation in the allogeneic group. There was no significant difference between the two groups after operation (t=-1.396, P=0.168). Tegner score increased from 4.07±1.39 to 6.43±1.14 in the autologous group and from 3.85±1.06 to 6.52±0.85 in the allogeneic group with no significant difference between the two groups after operation (t=-0.333, P=0.740). Stress radiographic showed that the talar tilt angle decreased from 15.60°±3.86° to 6.01°±2.64° in the autologous group, 16.99°±3.78° to 7.14°±3.34° in the allogeneic group, and there was no significant difference between the two groups after operation (t=-1.382, P=0.171). Anterior talar displacement reduced from 10.82±3.12 mm to 4.03±1.69 mm in the autologous group, from 10.10±2.02 mm to 4.17±1.52 mm in the allogeneic group, and there was no significant difference between the two groups after operation (t=-0.326, P=0.746). No donor tendon dysfunction was found in the autologous group. At the end of follow-up, there was no difference in ankle dorsiflexion, plantar flexion and hind foot mobility between autologous group and allogeneic group. Conclusion Arthroscopic autologous tendon and allogeneic tendon reconstruction of AFTL combined with CFL can obtain satisfactory short-term results. The autologous tendon group was superior to the allogeneic group in terms of fever, wound healing time. However, there was no significant difference in clinical effects between the two groups.

A pair of new tirucallane triterpenoid epimers, picraquassins M and N (1> and 2), were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were determined based on comprehensive spectroscopic and X-ray crystallographic analyses. In addition, their AChE inhibitory activity, cytotoxicity against five human tumour cell lines (SW480, MCF-7, HepG2, Hela, and PANC-1), and antimicrobial activity against two bacteria (Staphylococcus. aureus 209P and Escherichia coli ATCC0111) and two fungi (Candida albicans FIM709 and Aspergillus niger R330) were evaluated.

Background: Mental stress-induced myocardial ischemia (MSIMI) is closely associated with adverse cardiac events in patients with coronary artery disease (CAD) and we aimed to determine whether biomarkers and blood pressure could be potential predictors of MSIMI. Methods: This study enrolled 82 patients with documented CAD between June 1, 2017 and November 9, 2017. Patient blood samples were obtained at resting period and at the end of mental arithmetic. Then, patients were assigned to MSIMI positive group and MSIMI negative group. The main statistical methods included linear regression, receiver operating characteristic (ROC) curves, and logistic regression. Results: Patients with CAD with MSIMI had significantly greater median resting N-terminal pro-brain natriuretic peptide (NT-proBNP, 141.02 [45.85–202.76] pg/mL vs. 57.95 [27.06–117.64] pg/mL; Z = -2.23, P = 0.03) and mean systolic blood pressure (SBP) (145.56 ± 16.87 mmHg vs. 134.92 ± 18.16 mmHg, Z = -2.13, P = 0.04) when compared with those without MSIMI. After 5-min mental stress task, those who developed MSIMI presented higher elevation of median post-stressor high sensitivity cardiac troponin I (hs-cTnI, 0.020 [0.009–0.100] ng/mL vs. 0.009 [0.009–0.010] ng/mL; Z = -2.45, P = 0.01), post-stressor NT-proBNP (138.96 [39.93–201.56] pg/mL vs. 61.55 [25.66–86.50] pg/mL; Z = -2.15, P = 0.03) compared with those without MSIMI. Using the ROC curves, and after the adjustment for basic characteristics, the multiple logistic regression analysis showed that patients presenting a post-stressor hs-cTnI ≥ 0.015 ng/mL had seven-fold increase in the risk of developing MSIMI (odds ratio [OR]: 7.09; 95% confidence interval [CI]: 1.65–30.48; P = 0.009), a rest NT-proBNP ≥ 80.51 pg/mL had nearly eight-fold increase (OR: 7.85; 95% CI: 1.51–40.82; P = 0.014), a post-stressor NT-proBNP ≥ 98.80 pg/mL had 35-fold increase (OR: 34.96; 95% CI: 3.72– 328.50; P = 0.002), a rest SBP ≥ 129.50 mmHg had 11-fold increase (OR: 11.42; 95% CI: 1.21–108.17; P = 0.034). Conclusions The present study shows that CAD patients with higher hs-cTnI level, and/or greater NT-proBNP and/or SBP are at higher risk of suffering from MSIMI when compared with those without MSIMI, indicating that hs-cTnI, NT-proBNP, SBP might be potential predictors of MSIMI.