ABSTRACT
ObjectiveTo analyze the clinical and epidemiological characteristics of confirmed cases of human monkeypox infection in Changning District， Shanghai， and to explore their clinical and epidemiological characteristics. MethodsClinical data from 10 reported cases of monkeypox in individuals residing in Changning District or identified by local medical institutions between July 20 and September 30， 2023， were collected. Epidemiological case investigations were conducted， and throat swabs， anal swabs， and rash swabs were collected by the treating medical institutions. Real-time fluorescence quantitative PCR was used for monkeypox virus nucleic acid testing， and descriptive epidemiological analysis was applied to analyze the epidemiological characteristics of the cases. ResultsAll 10 confirmed cases of human monkeypox infection were all young males with an average age of 35.4 years， all of whom belonged to the men who have sex with men （MSM） population， with no occupational clustering. The primary clinical symptoms included fever， rash， enlarged inguinal lymph nodes， and muscle soreness. Nine cases presented with a rash， and seven cases experienced fever symptoms. Among the 10 cases， one experienced fever， rash， enlarged lymph nodes， and muscle soreness； two had fever， rash， and enlarged lymph nodes； two had fever， rash， and systemic soreness； two had only a rash； one had fever or rash； and one was asymptomatic. Among the nine cases with a rash， the rash was mainly localized to the genital or anal area， with fewer cases presenting rashes on the limbs or trunk simultaneously. All cases reported a history of non-exclusive MSM behavior within 21 days before the onset of the disease. The interval between the last suspected high-risk exposure and the onset of symptoms was 4 to 10 days， with an average interval of 6.9 days. The time from the onset of fever to the appearance of a rash was 0 to 5 days， with an average of 1.87 days. ConclusionThe main clinical manifestations of human infection with monkeypox are fever， rash， and enlarged inguinal lymph nodes. The MSM population is a high-risk group for monkeypox infection， and its source of infection may be associated with MSM exposure. Early-stage symptoms are mild， leading to potential underdiagnosis. Additionally， patients may conceal information during the investigation process， which increases the difficulty of epidemic prevention and control.
ABSTRACT
Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.
ABSTRACT
Objective@#To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) .@*Methods@#321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed.@*Results@#Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) .@*Conclusion@#MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.
ABSTRACT
Objective@#To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees.@*Methods@#Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated.@*Results@#320 subjects (47%) presented severe thrombocytopenia (PLT<50×109/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×109/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×109/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×109/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival.@*Conclusion@#PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.
ABSTRACT
Objective@#To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) .@*Methods@#112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed.@*Results@#Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ2=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model.@*Conclusion@#TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.
ABSTRACT
Objective To explore the role of the PI3K/Akt signaling pathway in the calvarial osteolysis induced by TCP wear particles in mice model.Methods Thirty-six male ICR mice were randomly divided into a sham group (n=12),TCP group (n=12)and a LY294002-treated group (n=12).A murine calvarial model of osteolysis was established through implanting 30 mg of TCP particles onto the surface of bilateral parietal bones following the removal of the periosteum.On the second postoperative day,LY294002 (5 mg·kg-1)was locally injected to the calvarium under the periosteum three times a week;mice in the sham group received local injection of normal saline (N.S.)in the calvarium,and the injection time was consistent with that of LY294002.Two weeks later,the calvaria and periostea were obtained after the mice were executed.The calvarial osteolysis,bone mineral density (BMD)and bone mineral content(BMC)were analyzed using Micro-CT,Hematoxylin-Eosin (HE)staining was conducted to observe the inflammatrory response and formation of osteoclasts.Real-time PCR was applied to detect the mRNA level of tartrate-resistant acid phosphatase (TRAP),the marker of osteoclasts formation,cathepsin K (CstK),receptor activator for nuclear factor-κB kigand (RANKL)and c-Fos.The release of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6)and IL-1β were measured using enzyme-linked immumsorbent assay (ELISA).Results Micro-CT and histological analysis indicated that LY294002,the specific inhibitor of PI3K,significantly prevented TCP wear particles-induced osteolysis and osteoclastogenesis,and increased BMD and BMC in the calvaria of mice.Real-time PCR data revealed LY294002 significantly suppressed the increase in mRNA level of osteoclastogenic genes such as TRAP,CstK,RANKL and c-Fos in the calvaria of TCP wear particles-implanted group.ELISA assay showed that TCP wear particles-induced release of TNF-α,IL-1β and IL-6 was significantly inhibited by LY294002 treatment.Furthermore,LY294002 significantly attenuated TCP wear particles-triggered activation of Akt,and down-regulated the level of p-AktSer473 and p-AktThr308.Conclusion PI3K/Akt signaling pathway contributes to TCP wear particle-induced osteolysis,and can be developed as a new therapeutic target for the prevention and treatment of bone destruction diseases caused by wear debris.
ABSTRACT
BACKGROUND:The Y-shaped mesh graft material weaved using lightweight polypropylen has the appropriate porosity, which not only can make the vaginal tissues grow and fuse rapidly on the mesh, but also can maintain good biological strength to ensure the fixed strength for the presacral suspension. OBJECTIVE:To retrospectively analyze the clinical effect of Y-shaped mesh for the biological function reconstruction of the female pelvic floor. METHODS:Ten female cases of pelvic floor dysfunction were enrol ed, aged 37-73 years, and al were given the treatment of sacral colposuspension under laparoscopy. Then perioperative complications were recorded;patients were fol owed up regularly to record the Pelvic Organ Prolapse Quantification (POP-Q) score at different time points;and the subjective satisfaction was investigated using the Pelvic Floor Impact Questionnaire (PFIQ-7). RESULTS AND CONCLUSION:After at least 6-month fol ow-up, no postoperative pelvic infection, nerve damage and complications appeared, the patients healed wel , and no mesh erosion, infection and other adverse reactions occurred. The POP-Q and PFIQ-7 scores at 1, 3 and 6 months after repair were significantly improved than those before repair (P<0.05). These results suggest that the Y-shaped biological mesh repairing female midpelvic floor dysfunction has good biocompatibility, and can restore the anatomy of the pelvic floor.