This article summarizes the domestic and international research progress of recombinant human follicle stimulating hormone(rFSH).According to relevant guidelines and application cases,the general requirements and common problems for non-clinical evaluation of rFSH are summarized.The clinical development prospects of long-acting rFSH products which is a hot research topic in recent years are analyzed and corresponding suggestions are given in order to provide reference for related work.

Objective To evaluate the molluscicidal effect and cost of spraying molluscicides with drones against Oncomelania hupensis snails in marshland and lake areas, so as to provide new insights into field snail control in China. Methods A marshland and lake setting measuring approximately 12 000 m² was selected in Wanzhi District, Wuhu City on June 2023 as the test field, and assigned to four groups, of 3 000 m² in each group. Environmental cleaning was not conducted in groups A or B, which were given 5% niclosamide ethanolamine salt granules sprayed with knapsack-type sprayers and drones at a dose of 40 g/m², and environmental cleaning was conducted in groups C and D, which were given 5% niclosamide ethanolamine salt granules sprayed with drones and knapsack-type sprayers at a dose of 40 g/m², respectively. O. hupensis snails were surveyed before chemical treatment and 1, 3, 5, 7, 14 days post-treatment. The uniformity of chemicals was determined on the day of treatment, and the snail mortality, corrected snail mortality and density of living snails were calculated and compared among groups. The cost of molluscicides, labor fees of environmental cleaning and chemical treatment and cost of equipment were calculated, and the cost for a 1% reduction in the mean density of living snails was calculated 14 days post-treatment. Results The mean densities of living snails and mortality rates of snails were 1.82 to 2.85 snails/0.1 m² and 1.41% to 2.94% in groups A, B, C and D before chemical treatment, and the mortality and corrected mortality of snails were 55.75%, 49.32%, 85.94% and 87.50%, and 55.00%, 48.47%, 85.70% and 87.29% in groups A, B, C and D 14 days post-treatment. There was a significant difference in the mortality of snails among the four groups 14 days post-treatment (χ² = 38.735, P < 0.005), and there was a higher snail mortality in Group D than in Group A (χ² = 16.876, P < 0.005), and higher in Group C than in Group B (χ² = 20.508, P < 0.005). The density of living snails reduced by 55.00%, 43.94%, 90.43% and 87.14% 14 days post-treatment relative to pre-treatment in groups A, B, C and D, respectively. The test for uniformity of chemicals showed that the mean dose of molluscicides were 57.34, 55.21, 40.19 g/m² and 32.37 g/m² in groups A, B, C and D, respectively, and the minimal standard deviation (7.07) and coefficient of variation (0.18) of mean doses were seen in Group C. The costs for chemical treatment were 0.33 Yuan in groups A and B and 1.53 Yuan in groups C and D, respectively. The costs for a 1% reduction in the mean density of living snails were 17.82, 22.47, 50.73 Yuan and 52.56 Yuan in groups A, B, C, and D 14 days post-treatment, respectively. Conclusions The molluscicidal effect and cost of spraying 5% niclosamide ethanolamine salt granules with drones are comparable to manual spraying, and chemical treatment with drones are high in uniformity of molluscicides, time- and labor-saving, and feasible for applications in complex environments, which deserves widespread applications in the field of snail control.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVES: To study the role of plasma exchange combined with continuous blood purification in the treatment of refractory Kawasaki disease shock syndrome (KDSS). METHODS: A total of 35 children with KDSS who were hospitalized in the Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, from January 2019 to August 2022 were included as subjects. According to whether plasma exchange combined with continuous veno-venous hemofiltration dialysis was performed, they were divided into a purification group with 12 patients and a conventional group with 23 patients. The two groups were compared in terms of clinical data, laboratory markers, and prognosis. RESULTS: Compared with the conventional group, the purification group had significantly shorter time to recovery from shock and length of hospital stay in the pediatric intensive care unit, as well as a significantly lower number of organs involved during the course of the disease (P<0.05). After treatment, the purification group had significant reductions in the levels of interleukin-6, tumor necrosis factor-α, heparin-binding protein, and brain natriuretic peptide (P<0.05), while the conventional group had significant increases in these indices after treatment (P<0.05). After treatment, the children in the purification group tended to have reductions in stroke volume variation, thoracic fluid content, and systemic vascular resistance and an increase in cardiac output over the time of treatment. CONCLUSIONS Plasma exchange combined with continuous veno-venous hemofiltration dialysis for the treatment of KDSS can alleviate inflammation, maintain fluid balance inside and outside blood vessels, and shorten the course of disease, the duration of shock and the length of hospital stay in the pediatric intensive care unit.
Humans ; Child ; Plasma Exchange ; Mucocutaneous Lymph Node Syndrome/therapy* ; Continuous Renal Replacement Therapy ; Renal Dialysis ; Plasmapheresis ; Shock

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.
Humans ; Epstein-Barr Virus Infections/diagnosis* ; Herpesvirus 4, Human/genetics* ; Retrospective Studies ; Viremia ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Lymphoproliferative Disorders/etiology* ; DNA, Viral ; Viral Load

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.
Humans ; Retrospective Studies ; Incidence ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hematologic Diseases/complications*

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease

Objective: To investigate whether admission blood pressure (BP) variability during multiple hospitalizations is associated with all-cause mortality independent of baseline BP in acute decompensated heart failure (ADHF). Methods: Patients with ADHF admitted to the Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University from September 2013 to December 2017 were retrospectively enrolled. The risk of all-cause mortality associated with indices of BP variability, including mean admission BPs, standard deviation of BP and coefficient of variation of BP during multiple hospitalizations was assessed, using Cox regression model. Results: A total of 1 006 ADHF patients (mean aged (69.3±13.5) years; 411 (40.8%) female; 670 (66.6%) with preserved ejection fraction) were enrolled. During a median follow-up of 1.54 years, 47.0% of patients died. In all ADHF patients, after adjusting for confounding factors, for every 1-standard deviation (SD) increase in SD and coefficient of variation (CV) of systolic BP, the risk of all-cause mortality increased by 10% and 11%, respectively (SD: HR, 1.10, 95%CI, 1.01-1.21, P=0.029, CV: HR, 1.11, 95%CI, 1.02-1.21, P=0.017); for every 1-SD increase in the mean of diastolic BP, the risk of all cause mortality decreased by 25% (HR, 0.75; 95%CI, 0.65-0.87; P<0.001). In ADHF patients with preserved ejection fraction, after accounted for potential confounders, higher SD and CV of admitted systolic and diastolic BP were significantly associated with higher risk of all-cause mortality, regardless of whether confounding factors were adjusted (P≤0.049); After adjusting for confounding factors, the risk of all-cause mortality increased by 18% and 19% for every 1-SD increase in SD and CV of systolic BP, while the risk of all-cause mortality increased by 11% and 15% for every 1-SD increase in SD and CV of diastolic BP. In ADHF patients with reduced ejection fraction, after adjusting for confounding factors, the higher the mean admission systolic BP during multiple hospitalizations, the lower the risk of total mortality (HR, 0.68; 95%CI, 0.47-1.00; P=0.049). Conclusions: In patients with ADHF, independent of baseline BP, BP variability during multiple hospitalizations was strong predictor of all-cause mortality.
Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Blood Pressure ; Retrospective Studies ; Heart Failure ; Hospitalization ; Ventricular Dysfunction, Left ; Risk Factors ; Prognosis