Objective:To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) .Methods:Continuous cases of R/R AML treated with the CLAG+DAC protocol or CLAG alone at the First Affiliated Hospital of Soochow University from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, individual treatment regimen, treatment effect, disease progression, and survival status of patients were recorded. The factors influencing the efficacy of the CLAG±DAC chemotherapy regimens were analyzed, and the overall survival (OS) time after reinduction was calculated using the Kaplan-Meier method.Results:This study included a total of 53 patients, with 33 male patients and an average age of 40.6 years. Thirty-three patients achieved complete remission (CR+CRi) of the disease after the CLAG±DAC chemotherapy regimen and six patients achieved partial remission (PR), while 14 did not. Thirty-two patients eventually underwent hematopoietic stem cell transplantation, and the median OS of the patients was 55.9 months until follow-up. Patients with disease remission after the application of the CLAG±DAC chemotherapy had a significantly longer survival time than those without remission ( P<0.001). The results of the multifactorial analysis have revealed that combined DAC ( OR=4.60, 95% CI 1.14-23.5, P=0.04) and DNMT3A mutation ( OR=0.14, 95% CI 0.01-0.89, P=0.05) were the factors influencing the efficacy of the CLAG±DAC chemotherapy regimen. The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen ( OR=10.84, 95% CI 1.48-288.50, P=0.04) . Conclusion:The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

Objective:To explore the role and mechanism of IL-39 in K562 cells.Methods:The expressions of IL-39R and STAT1/STAT3 in K562 cells were detected via qRT-PCR;the protein levels of phospho-STAT1/STAT3 and STAT1/STAT3 in K562 cells were detected by Western blot;the mRNA regulated by IL-39 in K562 cells was predicted by RNA sequencing.Results:rIL-39 significantly promoted the expression of IL-39R in K562 cells;IL-39 affected K562 cells through STAT1 pathway;IL-39 significantly regulated the expression of mRNA in K562 cells,thus potentially affecting a series of biological processes.Conclusion:IL-39 can directly act on K562 cells,alter gene transcriptional expression and inhibit tumor growth through the STAT1 pathway.IL-39 may similarly modulate gene expression profile in human leukemia cells.

To evaluate the application value of metal clip combined with suture and rubber coil as a simple traction device in endoscopic submucosal dissection (ESD) for intestinal mucosal lesions, a total of 56 patients with early colonic cancer and precancerous lesions who received ESD in Jiangyin People's Hospital from January 2021 to July 2022 were randomly divided into the control group ( n=28, conventional ESD) and the traction group ( n= 28, suture and rubber coil as a simple traction device). The total time of ESD, mucosal dissection time, number of submucosal injections, complete resection rate and complications were compared between the two groups. The operation time of the traction group was shorter than that of the control group (74.64±33.25 min VS 117.18±35.75 min, t=4.61, P<0.001). The desection time of mucosa in the traction group was shorter than that in the control group (51.61±24.87 min VS 99.11±32.73 min, t=6.11, P<0.001). The number of submucosal injection in the traction group was less than that of the control group with significant difference (1.68±1.16 VS 4.96±1.41, t=9.57, P<0.001). There was no significant differences in operation area, complete resection rate or complication between the two groups ( P>0.05). The traction assistance technology of metal clip combined with suture and rubber coil can reduce the technical difficulty of colonic ESD and shorten the operation time.

Objective:To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Objective:To evaluate the efficacy of botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy.Methods:Twenty cases (40 sides) of masseter hypertrophy were injected with botulinum toxin A, among which 10 cases were taken as experimental group and the other 10 cases as control group. The experimental group had preoperative ultrasound examination to measure the thickness of masseter, and use ultrasound-guided precise injection during the operation, and then ultrasound recheck to measure the postoperative masseter thickness; The other 10 cases of control group adopt traditional 3-point injection method.Results:The masseter thickness of the two groups at different period of times after treatment was decreased ( P<0.001), the most obviously decrease happened 4-12 weeks after injection. The mean reduction was 26.8% at 4 weeks and 28.4% at 12 weeks after injection. Masseter muscle thickness recovered by 22% at 24 weeks and by 20% at 36 weeks. The average follow-up was 6.0±2.4 months with no serious complications occurred. In the control group, there was a partial masseter bulge in one case. The satisfactory rate of the patients in the experimental group was higher than that of the control group. Conclusions:Botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy is an effective treatment, which is more accurate and effective than the traditional injection method.

Objective:To analyze the epidemiological and clinical characteristics of hospitalized patients with dengue fever in Guangdong Province in 2019, so as to provide reference for clinical diagnosis and treatment of dengue fever.Methods:The general data, laboratory examination data, clinical manifestations and prognosis data of 480 inpatients with dengue fever admitted to Eight People′s Hospital Affiliated to Guangzhou Medical University between January 4 and October 31, 2019 were analyzed retrospectively. The clinical and onset characteristics of patients with dengue fever were described.Results:Among 480 dengue patients, 442(92.1%) were dengue fever, 38(7.9%) were severe dengue, and 136(28.3%) had underlying diseases. The peak age of onset was mainly in young adults aged 20 to 49 years old, accounting for 66.0%(317/480) in total. The seasonal peak was mainly in August to October. There were 399(83.1%) local cases and 61(12.7%) imported cases. The most common clinical manifestations were fever (98.1%, 471/480), chills (72.9%, 350/480), headache (58.5%, 281/480) and bone/joint/muscle pain (67.1%, 322/480), followed by digestive tract symptoms and respiratory tract symptoms. Among 446 serum samples, 358 (80.3%) were dengue virus (DENV)-1, 54 (12.1%) were DENV-2, 34 (7.6%) were DENV-3. The main laboratory tests of the patients were leucopenia (65.8%, 316/480), low hematocrit (30.2%, 145/480), thrombocytopenia (48.3%, 232/480), neutropenia (44.8%, 215/480), elevated alanine aminotransferase (ALT) (37.7%, 181/480) and aspartate aminotransferase (AST) (59.4%, 285/480). Treatment mainly adopted symptomatic support treatment and active prevention of complications. The length of stay was (5.8±3.1) days (range 1.0-38.0 days). A total of 461(96.0%) patients were cured or improved.Conclusions:In 2019, the majority of dengue fever patients in Guangdong Province are young adults aged 20 to 49 years old, and the proportion of severe patients is high, with DENV-1 infection as the main type. After symptomatic support treatment and active prevention of complications, most of the dengue fever patients have a good prognosis.

Objective:To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation.Methods:The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed.Results:Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different ( P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant ( P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant ( χ2= 4.694, P = 0.030; χ2= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR 1 state, and 2 patients with recurrence after transplantation obtained CR 2 after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion:Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis

Objective:To investigate the clinical characteristics and CT imaging features of patients with different clinical types of coronavirus disease 2019 (COVID-19), so as to provide a reference for the treatment and evaluation of COVID-19.Methods:The clinical data of 278 patients with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20th to February 10th in 2020 were collected. The patients were divided into mild, ordinary, severe and critical types. The differences of clinical symptoms and signs, laboratory examination indexes and CT image features of lung in different clinical types were analyzed and compared, and the relationship between clinical and imaging features and clinical types of diseases were analyzed.Results:Among the 278 patients with COVID-19, 130 were male (46.8%) and 148 were female (53.2%), of whom 88.8% (247/278) were 20 to 69 years old. 238 (85.6%) patients combined one or more basic diseases. The source of cases was mainly imported cases ( n = 201, 72.3%), of whom 89 cases were imported from Wuhan, accounting for 44.3% of all imported cases. With the aggravation of the disease, the male composition ratio, age and the number of basic diseases of patients gradually increased, and the incidences of fever, dry cough, chilly or chills, and fatigue in severe and critical patients were significantly higher than those in the mild and ordinary ones. The white blood cell count (WBC), neutrophil counts (NEU) and proportions (NEU%) of the severe and critical patients were higher than those of the mild and ordinary patients [WBC (×10 9/L): 5.7±3.1, 6.5±2.4 vs. 5.4±1.7, 4.9±1.6; NEU (×10 9/L): 4.4±3.1, 4.9±2.5 vs. 2.8±1.2, 2.9±1.3; NEU%: 0.72±0.13, 0.73±0.14 vs. 0.51±0.12, 0.59±0.11; all P < 0.01], while the lymphocyte count (LYM) and ratio (LYM%), platelet count (PLT) were lower than those in the mild and ordinary patients [LYM (×10 9/L): 1.0±0.4, 1.2±0.8 vs. 2.1±0.9, 1.5±0.6; LYM%: 0.21±0.11, 0.20±0.12 vs. 0.40±0.11, 0.32±0.11; PLT (×10 9/L): 177.1±47.8, 157.7±51.6 vs. 215.3±59.7, 191.8±64.3; all P < 0.05]. The level of albumin (Alb) was the lowest in the critical patients and the level of total bilirubin (TBil) was the highest, which was statistically significant as compared with the mild, ordinary and severe patients [Alb (g/L): 33.0±5.8 vs. 42.8±4.4, 39.6±5.1, 34.4±4.2; TBil (μmol/L): 20.1±12.8 vs. 12.0±8.7, 10.9±6.3, 12.2±8.3; both P < 0.01]. Lactate dehydration (LDH) and cardiac troponin I (cTnI) in the severe and critical patients were significantly higher than those in the mild and ordinary patients [LDH (μmol·s -1·L -1): 5.6±2.2, 5.0±2.9 vs. 2.8±0.9, 3.3±1.2; cTnI (μg/L): 0.010 (0.006, 0.012), 0.010 (0.006, 0.012) vs. 0.005 (0.003, 0.006), 0.005 (0.001, 0.008); both P < 0.05]. C-reactive protein (CRP) level of severe patients were higher than that in the mild, ordinary and critical patients [mg/L: 43.3 (33.2, 72.1) vs. 22.1 (16.2, 25.7), 29.7 (19.8, 43.1), 25.8 (23.0, 36.7), P < 0.01]. The level of procalcitonin (PCT) in the severe and critical patients was higher than that in the mild and ordinary patients [μg/L: 0.17 (0.12, 0.26), 0.13 (0.09, 0.24) vs. 0.06 (0.05, 0.08), 0.05 (0.04, 0.09), P < 0.01]. The typical CT imaging features were as follows: the ordinary type mainly showed the single or multiple ground glass shadows on the chest image; the severe type mainly showed the multiple ground glass shadows, infiltration shadows or solid transformation shadows. Compared with the ordinary patients, the lesions increase, and the scope of the lesion expanded to show double lungs. Critical type was mainly manifested as diffuse consolidation of both lungs with multiple patchy density increase shadows, multiple leafy patchy density increase shadows were seen on each leaf, most of them were ground glass-like density, and some were shown separately lung consolidation. Conclusions:Men, advanced aged, and combining multiple underlying diseases are high-risk populations of COVID-19, and they should pay close attention to the risk of progressing to severe or critical type. CT imaging features could be used as an important supplement when diagnosing severe and critical COVID-19.