[Three cases of occupational acute trimethyltin chloride poisoning].

Trimethyltin chloride is a highly toxic substance, which is absorbed through respiratory tract, skin and digestive tract, with central nervous system injury as the main clinical manifestations, and can be accompanied by damage to various organs. In this paper, the treatment process of 3 patients with acute trimethyltin chloride poisoning was reviewed, and their clinical manifestations, auxiliary examination, diagnosis and treatment were analyzed. Three patients were misdiagnosed as mental abnormality, encephalitis, and hepatic encephalopathy in different hospitals in the early stage of medical treatment, suggesting that clinicians should pay attention to the occupational contact history of poisoned patients and conduct toxicant detection in time to avoid misdiagnosis and mistreatment.

[Restratifying the prognosis of acute myeloid leukemia patients with CEBPA double mutations based on CSF3R mutations and measurable residual disease].

Objective: This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) . Methods: The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information. Results: Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations (HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations (HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations (HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis (P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS (P<0.001) and OS (P=0.006) . Conclusion: Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.

[Venetoclax with low-dose cytarabine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy: results from the Chinese cohort of a phase three randomized placebo-controlled trial].

Objective: To investigate the safety and efficacy of venetoclax with low-dose cytarabine (LDAC) in Chinese patients with acute myeloid leukemia (AML) who are unable to tolerate intensive induction chemotherapy. Methods: Adults ≥ 18 years with newly diagnosed AML who were ineligible for intensive chemotherapy were enrolled in this international, randomized, double-blind, placebo-controlled trial. Globally, patients (n=211) were randomized 2∶1 to either venetoclax with LDAC or placebo with LDAC in 28-d cycles, with LDAC on days 1-10. The primary endpoint was OS; the secondary endpoints included response rates, event-free survival, and adverse events. Results: A total of 15 Chinese patients were enrolled (venetoclax arm, n=9; placebo arm, n=6) . The median age was 72 years (range, 61-86) . For the primary analysis, the venetoclax arm provided a 38% reduction in death risk compared with the placebo[hazard ratio (HR) , 0.62 (95%CI 0.12-3.07) ]. An unplanned analysis with an additional 6 months of follow-up demonstrated a median OS of 9.0 months for venetoclax compared with 4.1 months for placebo. The complete remission (CR) rates with CR with incomplete blood count recovery (CRi) were 3/9 (33%) and 0/6 (0%) , respectively. The most common non-hematologic adverse effects (venetoclax vs placebo) were hypokalemia[5/9 (56%) vs 4/6 (67%) ], vomiting[4/9 (44%) vs 3/6 (50%) ], constipation[2/9 (22%) vs 4/6 (67%) ], and hypoalbuminemia[1/9 (11%) vs 4/6 (67%) ]. Conclusion: Venetoclax with LDAC demonstrated meaningful efficacy and a manageable safety profile in Chinese patients consistent with the observations from the global VIALE-C population, making it an important treatment option for patients with newly diagnosed AML who are otherwise ineligible for intensive chemotherapy.

Effects of probiotics on intestinal flora, inflammation and degree of liver cirrhosis in rats with liver cirrhosis by regulating Wnt/ß-catenin signaling pathway.

We aimed to explore the effects of probiotics on intestinal flora, inflammation and degree of liver cirrhosis in rats with liver cirrhosis, and to verify the Wnt/ß-catenin signaling pathway that regulates this process. A total of 30 SD rats were randomly divided into 3 groups, namely, control group (n=10), model group (n=10) and probiotic group (n=10). Rats in the model group were used to construct liver cirrhosis models using carbon tetrachloride (CCL4) method, and those in the probiotic group were administered with probiotic preparations by gavage for 8 weeks. Then the feces of rats in each group were taken to detect the composition of intestinal flora, and changes in the content of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and interferon-gamma (IFN-γ), in peripheral blood collected were examined by enzyme-linked immunosorbent assay (ELISA). Next, changes in the degree of liver cirrhosis were analyzed by hematoxylin and eosin (H&E) staining, and the expression levels of the Wnt/ß-catenin signaling pathway-related molecules, including ß-catenin, glycogen synthase kinase (GSK)-3ß and Frizzled-2, in liver tissues in each group were detected via polymerase chain reaction (PCR) and Western blotting (WB). Compared with rats in the control group, those in the model group had a disordered structure of hepatic lobule and hyperplasia of a large number of fibrous tissues. In contrast to those in the model group, the liver lobule structure was greatly improved, the edema cells were obviously reduced, and the hyperplasia of collagen fibers was remarkably alleviated in the probiotic group. Moreover, the degree of liver cirrhosis in the probiotic group was significantly reduced compared with that in the model group. Moreover, the rats in the model group exhibited a higher Bifidobacterium level in the intestinal tract, while those in the probiotic group displayed higher levels of microorganisms in the intestinal tract, such as Lachnospiraceae, Ruminococcaceae, Actinbacteria, Slackia and Pasteurellaceae. In comparison with that in the control group, the level of salt-tolerant Lactobacillus in the intestinal tract of rats in the model group was significantly decreased, while that in the probiotic group was partially increased (P=0.023). Meanwhile, some intestinal flora of rats in the control group, model group and probiotic group were closely correlated. Specifically, highly positive correlations were found between Bacteroidetes and Paraeggerthella (r=0.423, P=0.034) and between Firmicutes and Lactobacillus (r=0.318, P=0.027), but strongly negative associations were detected between Firmicutes and Paraeggerthella (r=-0.691, p=0.004) and between Paraeggerthella and Lactobacillus (r=-0.384, P=0.047). In addition, the levels of inflammatory cytokines TNF-α IL-6, MCP-1 and IFN-γ in the plasma of rats in the model group were markedly higher than those in the control group (P<0.05), whereas such levels in the probiotic group were decreased compared with those in the model group (P<0.05). PCR results revealed that the expression levels of ß-catenin and Frizzled-2 in the model group were higher than those in the control group, whereas they were lower in the probiotic group than those in the model group (P<0.05). Furthermore, the model group had a decreased level of GSK-3ß in comparison with the control group, but the probiotic group had a higher level of GSK-3ß than the model group (P<0.05). WB results were consistent with PCR results. Probiotics can affect intestinal flora, inflammation and degree of liver cirrhosis in rats with liver cirrhosis, and its mechanism may be related to the Wnt/ß-catenin signaling pathway.

Fibulin-5 protects the extracellular matrix of chondrocytes by inhibiting the Wnt/ß-catenin signaling pathway and relieves osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a common disease in the elderly and seriously affects the quality of life of patients. The purpose of this study was to explore the protective effect of Fibulin-5 on articular chondrocytes and its mechanism of action. PATIENTS AND METHODS: Articular cartilage tissues from patients with OA and normal people were selected and tested for differences in Fibulin-5 expression. In addition, human chondrocytes were cultured, and the effects of Fibulin-5 on the extracellular matrix (ECM) of chondrocytes and the level of inflammation were examined by means of cell transfection and cytokine intervention. SKL2001, an agonist of the Wnt/ß-catenin signaling pathway, was used to validate the mechanism of action of Fibulin-5 to protect chondrocytes. RESULTS: Fibulin-5 was lowly expressed in the cartilage tissue of patients with OA. Overexpression of Fibulin-5 significantly increased the expressions of ECM collagen II and aggrecan in chondrocytes, while decreasing the expressions of MMP-3 and MMP-13. In addition, Fibulin-5 reduced IL-1ß-induced inflammation of chondrocytes, as well as expressions of IL-6, IL-8, and TNF-α. Overexpression of Fibulin-5 also reduced the activity of Wnt/ß-catenin signaling pathway, and activation of Wnt/ß-catenin signaling pathway attenuated the protective effects of Fibulin-5 on the ECM of chondrocytes. CONCLUSIONS: Fibulin-5 can protect the ECM of chondrocytes and reduce the inflammatory response of chondrocytes by inhibiting the Wnt/ß-catenin signaling pathway.

[Prognostic analysis of 182 newly diagnosed multiple myeloma patients with high risk cytogenetic abnormalities].

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.

[The prognostic significance of dynamic monitoring of minimal residual disease (MRD) status in patients with newly-diagnosed multiple myeloma].

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

[Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients].

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

[Clinical study of a new wearable device for rehabilitation after total knee arthroplasty].

Objective: To evaluate the effect of promoting knee joint rehabilitation after total knee arthroplasty (TKA) with a rehabilitation training instrument NEO-GAIT. Methods: Sixty patients who received TKA from January 2017 to July 2017 in the Third Hospital of Hebei Medical University were randomly assigned to receive rehabilitation training with continuous passive motion (CPM) or NEO-GAIT with random number (30 cases in CPM group, included 8 males and 22 females; 30 cases in NEO-GAIT group, included 6 males and 24 females). The visual analogue scale (VAS) evaluation of pain, the postoperative range of motion (ROM) of the knee at the 5th and 10th day, and the Hospital for Special Surgery Knee-rating Score (HSS) at 1-month and 3-month follow-up were recorded. The data were compared between the two groups with paired t test. Results: All the patients were followed-up for more than 3 months. The mean VAS in CPM group and NEO-GAIT group on the 5th day was 2.4±1.1, 2.8±1.3, respectively; and it was 2.1±1.1, 2.5±1.2 respectively on the 10th day after the operation (t=-1.618, -1.505, both P>0.05). There was no significant difference in ROM on the 5th day after operation between the 2 groups (84°±12° vs 85°±12°, t=-0.377, P>0.05); however, it was remarkably higher in the NEO-GAIT group (95°±11°) than that in CPM group (88°±8°) on the 10th day after the operation (t=-3.002, P<0.05). The HSS score at 1-month follow-up in CPM group was 72±9, and it was 84±10 in NEO-GAIT group (t=-5.358, P<0.05); but it was comparative between the two groups at the 3-month follow-up (87±5 vs 89±5, t=-1.575, P>0.05). Conclusion: NEO-GAIT plays a more active and effective role in promoting postoperative rehabilitation after TKA than CPM.

[Clinical significance of loop electrosurgical excisional procedure in diagnosis and treatment of cervical adenocarcinoma in situ and invasive cervical adenocarcinoma].

Objective: To evaluate the accuracy of colposcopic biopsy on diagnosis of cervical adenocarcinoma in situ (AIS) and the clinical significance of loop electrosurgical excisional procedure (LEEP) on diagnosis and treatment of AIS and invasive adenocarcinoma. Methods: All medical records of 193 patients diagnosed as AIS by colposcopic biopsy and (or) AIS or invasive adenocarcinoma diagnosed by LEEP conization from Jan. 2015 to Dec. 2016 in Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. The final diagnosis was based on colposcopic biopsy or LEEP or the highest grade of pathological diagnosis after hysterectomy. Results: In the 193 patients, 155 cases were finally diagnosed as AIS and 38 cases as invasive adenocarcinoma by histopathologic examination. Among the 155 AIS patients, 21.9% (34/155) had positive cone margins, in which 26 patients had hysterectomy, 30.8% (8/26) had residual disease in hysterectomy specimens; 78.1% (121/155) had negative cone margins, 68 patients with negative margins had hysterectomy and 5.9% (4/68) had residual disease, which was significantly lower than that with positive margins (χ(2)=10.46, P=0.001) . One hundred and twenty from one hundred ninty-three (62.3%, 120/193) with AIS were detected by colposcopy. Pathological diagnosis of 50.8% (98/193) cases were upgraded after LEEP conization. Conclusions: Colposcopy is indispensable for the diagnosis of AIS, but accurate diagnosis should be made by LEEP. LEEP is capable of detecting AIS or cervical adenocarcinoma that was misdiagnosed by colposcopy, which is a pivotal method for accurate diagnosis. The margin status of LEEP is important for patients in choosing further hysterectomy, but the presence of cervical adenocarcinoma should always be aware of.

DNA Barcoding for Identification of Sugarcane Borers in China.

Sugarcane borers are economically damaging insects with species that vary in distribution patterns both geographically and temporally, and vary based on ecological niche. Currently, identification of sugarcane borers is mostly based on morphological characters. However, morphological identification requires taxonomic expertise. An alternative method to identify sugarcane borers is the use of molecular data. DNA barcoding based on partial cytochrome c oxidase subunit 1 (COI) sequences has proven to be a useful tool for rapid and accurate species determination in many insect taxa. This study was conducted to test the effectiveness of DNA barcodes to discriminate among sugarcane borer species in China. Partial sequences of the COI gene (709 bp) were obtained from six species collected from different geographic areas. Results showed that the pairwise intraspecies genetic distance was < 0.02, whereas the interspecies genetic distance ranged from 0.117 to 0.182. Results from a neighbor-joining tree showed that the six sugarcane borer species were certainly separated. These results suggested that the partial COI sequences had high barcoding resolution in discriminating among sugarcane borer species. Our study emphasized the use of DNA barcodes for identification of the analyzed sugarcane borer species and represents an important step for building a comprehensive barcode library for sugarcane borers in China.

[A retrospective study of the BiRd regimen in the treatment of relapsed/ refractory multiple myeloma].

Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6 (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated. Conclusion: The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.