Temporal and spatial variations in the sub-daily precipitation structure over the Qinghai-Tibet Plateau (QTP).

Precipitation is a vital component of the global atmospheric and hydrological cycles and influencing the distribution of water resources. Even subtle changes in precipitation can significantly impact ecosystems, energy cycles, agricultural production, and food security. Therefore, understanding the changes in the precipitation structure under climate change is essential. The Qinghai-Tibet Plateau (QTP) is a region sensitive to global climate change and profoundly impacts the atmospheric water cycle in Asia and even globally, rendering it a hot topic in climate change research in recent years. Few studies have examined on the sub-daily scale precipitation structure over the QTP. In this paper, the characteristics of sub-daily precipitation on the QTP were systematically investigated from multiple perspectives, including the concentration index, skewness (the third standardized moment of a distribution), and kurtosis (the fourth standardized moment of a distribution). The results indicated that the frequency of moderate-intensity nighttime precipitation on the QTP generally increased, and the analysis of both the concentration index and kurtosis (skewness) suggested that extreme precipitation was more frequent in the southwestern foothills of the QTP. Furthermore, potential high-risk areas for natural disasters were identified on the QTP, and found that the southeastern part of the plateau constituted a potential hotspot area for flood disasters. Given the complexity of climate change, a comprehensive analysis of the spatiotemporal characteristics of diurnal and nighttime precipitation changes on the QTP could help reveal the regularity of precipitation changes. This has significant implications for forecasting, warning, disaster preparedness, and mitigation efforts on the QTP.

Anlotinib combined with chemotherapy and immunotherapy for advanced pulmonary sarcomatoid cancer: a case report and literature review.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare disease which is highly malignant with a poor prognosis. PSC is highly resistant to chemotherapy and radiotherapy and is prone to recurrence even after surgery. Most of what is known about PSC comes from limited single-center, retrospective studies. There is still no standard international clinical guideline for PSC. Limited case reports have shown that PSC patients with driver gene mutations and high programmed death-ligand 1 (PD-L1) expression have good responses to molecular targeted therapy and immune checkpoint inhibitor (ICI) immunotherapy, respectively. Therefore, current first-line chemotherapy, targeted therapy and immunotherapy play a leading role in the diagnosis and treatment of advanced PSC patients. Case Description: We report a 42-year-old male who was diagnosed with PSC [stage IVB (T4N2M1)] and treated at our department (Department of Radiation Oncology, The Affiliated Hospital of Soochow University). The initial computed tomography (CT) scan of the chest showed a large mass (159 mm × 112 mm) which on needle biopsy showed sarcomatoid carcinoma histology. The patient received 8 cycles of abraxane plus cisplatin chemotherapy combined with anlotinib and immunotherapy, followed by immunotherapy and anlotinib for >1 year. Finally, the local tumor was well controlled, and no obvious drug-related adverse reactions were observed. The large lesions in the lung remained in complete response for >24 months. Conclusions: To our knowledge, this is the first reported case of an advanced PSC patient showing a good response to the treatment consisting of anlotinib combined with sintilimab and platinum-doublet chemotherapy. This case suggests that chemotherapy combined with antiangiogenic therapy and immunotherapy may benefit patients with advanced PSC. Long-term immunotherapy and anlotinib maintenance therapy has been safe and effective in our case. However, randomized controlled clinical studies are needed to confirm the efficacy and safety of these treatment options.

Epigenetic therapy with chidamide alone or combined with 5­azacitidine exerts antitumour effects on acute myeloid leukaemia cells in vitro.

Chidamide, a selective histone deacetylase inhibitor, has antitumour effects. 5­azacitidine (5­AZA), a hypomethylating agent, is effective in treating acute myeloid leukaemia (AML) and myelodysplastic syndrome. However, to the best of our knowledge, the effect of chidamide and 5­AZA on AML cell lines has not been fully investigated. In the present study, the antileukaemia activity of chidamide, alone and in combination with 5­AZA, was assessed on different subtypes of AML cell lines (M1­M5) and primary samples from several patients with AML in vitro. The results indicated that the proliferation of leukaemia cells was significantly and dose­dependently inhibited by chidamide and 5­AZA alone or in combination. The combination also had marked synergistic effects to induce apoptosis of AML cells. The apoptosis of leukaemia cells was induced via downregulation of BCL­2 and myeloid­cell leukemia 1 (MCL­1) levels. Of note, chidamide also degraded the MCL­1 protein in venetoclax­resistant U937 cells, in which the MCL­1 protein is upregulated. In addition, chidamide was able to induce myeloid differentiation (with CD11b upregulation) of AML cell lines or monocytic/dendritic differentiation (with CD86 upregulation) of primary cultured cells from several patients with AML. Chidamide was also able to promote the differentiation of the venetoclax­resistant U937 cell line by upregulating CD11b expression. In conclusion, chidamide alone or combined with 5­AZA may be an effective therapy for AML.

Efficiency of anti-VEGF therapy in central nervous system AML relapse: A case report and literature review.

There have been few reports on the treatment of central nervous system (CNS) acute myeloid leukemia (AML) relapse. This case study demonstrates that bevacizumab may be a viable treatment option when combined with IT chemotherapy as maintenance therapy for those with CNS leukemia.

The Clinical and Molecular Characteristics of FLT3 Mutations in Chinese De Novo Adolescent and Adult Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are frequent in acute myeloid leukemia (AML) and have important prognostic and therapeutic implications. FLT3 aberrations have been detected in a smaller fraction of acute lymphoblastic leukemia (ALL), and their prognostic value is not well established. We therefore assessed the FLT3 mutation in Chinese adolescent and adult ALL patients. PATIENTS AND METHODS: We have examined a cohort of 117 Chinese de novo adolescent and adult ALL patients enrolled between June 2016 and June 2017 from the First Affiliated Hospital of Soochow University. Prognostic factors for the ALL patient population were estimated by the Cox regression method. FLT3 mutation was detected by PCR, and its clinical effect was assessed by Kaplan-Meier curves. Differences in FLT3 mutation rate between subgroups were tested by chi-square test. RESULTS: FLT3 mutations accounted for 6.8% (8/117) in our cohort, including 3 internal tandem duplications (2.6%) and 5 tyrosine kinase domains (4.3%, 3 D835Y mutations, 1 M664I mutation, and 1 I867S mutation), which had no clinical significance on either overall survival (OS) or event-free survival. Alterations in FLT3 occurred more often in early thymic precursor (ETP)-ALL compared to non-ETP T-cell acute lymphoblastic leukemia (P = .028). However, the age at onset (P = .004), initial platelet counts (P = .018), and transplantation status (P = .007) were independent prognostic factors of OS for ALL in multivariate analysis. CONCLUSION: The FLT3 mutation was not common in Chinese ALL patients. Age at onset, platelet counts, and transplantation status rather than the presence of the FLT3 mutation were independent prognostic variables for ALL on OS in our cohort. Despite our small sample size, ETP-ALL may indicate a comparable higher FLT3-mutant rate. Because ETP-ALL has been identified as high-risk subgroup, these data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic hematopoietic stem-cell transplantation for FLT3-mutant ETP-ALL.

FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells.

BACKGROUND: Cervical cancer is one of the most common causes of cancer-associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy. METHODS: Western blot was applied to determine the expression of FEN1- and apoptosis-related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo. RESULTS: Our data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo. CONCLUSION: FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell.

Transcriptome Analysis of FEN1 Knockdown HEK293T Cell Strain Reveals Alteration in Nucleic Acid Metabolism, Virus Infection, Cell Morphogenesis and Cancer Development.

AIM AND OBJECTIVE: Flap endonuclease-1 (FEN1) plays a central role in DNA replication and DNA damage repair process. In mammals, FEN1 functional sites variation is related to cancer and chronic inflammation, and supports the role of FEN1 as a tumor suppressor. However, FEN1 is overexpressed in multiple types of cancer cells and is associated with drug resistance, supporting its role as an oncogene. Hence, it is vital to explore the multi-functions of FEN1 in normal cell metabolic process. This study was undertaken to examine how the gene expression profile changes when FEN1 is downregulated in 293T cells. MATERIALS AND METHODS: Using the RNA sequencing and real-time PCR approaches, the transcript expression profile of FEN1 knockdown HEK293T cells have been detected for the next step evaluation, analyzation, and validation. RESULTS: Our results confirmed that FEN1 is important for cell viability. We showed that when FEN1 downregulation led to the interruption of nucleic acids related metabolisms, cell cycle related metabolisms are significantly interrupted. FEN1 may also participate in non-coding RNA processing, ribosome RNA processing, transfer RNA processing, ribosome biogenesis, virus infection and cell morphogenesis. CONCLUSION: These findings provide insight into how FEN1 nuclease might regulate a wide variety of biological processes, and laid the foundation for understanding the role of other RAD2 family nucleases in cell growth and metabolism.

[Accumulation and Biotransformation in Typical Freshwater Algae Species Influenced by Titanium Dioxide Nanoparticles Under Long-term Exposure].

In the present study, the accumulation and biotransformation of arsenate in typical freshwater algae species were examined under long-term influence of titanium dioxide nanoparticles (nano-TiO2). Results showed that different algae species had largely varied capacities of accumulation and biotransformation of arsenate. The arsenic accumulation reached (819.66±11.25) µg·g-1 DW in Scenedesmus obliquus, which was higher than that in Microcystis aeruginosa of (355.95±8.31) µg·g-1 DW. Nano-TiO2 increased arsenic accumulation in these exposed algae species, and then reduced arsenic levels in the relative culture media. Furthermore, nano-TiO2 improved arsenic biotransformation in the exposed algae, and the organic arsenic was dimethylarsinous acid (DMA) and monomethylarsonous acid (MMA) in Microcystis aeruginosa and Scenedesmus obliquus, respectively. Additionally, the release of organic arsenic was lower from the exposed algae in nano-TiO2 treatments than in the control, indicating that nano-TiO2 couldn't stimulate the release of organic arsenic from algae under long-term exposure. These results could improve insights on the ecological risk of nano-TiO2 associated with arsenic in the environment.

Fitness is Recovered with the Decline of Dimethachlon Resistance in Laboratory-induced Mutants of Sclerotinia sclerotiorum after Long-term Cold Storage.

After four years of cold storage, dimethachlon resistance of two laboratory-induced resistant Sclerotinia sclerotiorum isolates SCG7 and LA50 declined by 99.5% and 98.9%, respectively, and cross resistance to iprodione and procymidone also declined dramatically. Along with the decline of fungicide resistance, osmotic sensitivity to sodium chloride and glucose decreased tremendously; mycelial growth rate, sclerotia number and weight per potato dextrose agar (PDA) plate increased on average by 118.6%, 85. 5% and 64.5%, respectively; and virulence to detached leaves of oilseed rape increased by 72.7% on average. Significant negative correlations were detected between dimethachlon resistance levels and mycelial growth rate on PDA (r = -0.980, P = 0.021), and between resistance levels and lesion diameters on detached leaves of oilseed rape plants (r = -0.997, P = 0.002). These results have profound implications for assessing the potential risk for resistance development to dicarboximide fungicides in S. sclerotiorum.

Baseline Sensitivity of Pyraclostrobin and Toxicity of SHAM to Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a cosmopolitan plant pathogen notable for its wide host range. The quinone outside inhibitor (QoI) fungicide pyraclostrobin has not been registered for control of S. sclerotiorum in China. In this study, baseline sensitivity of pyraclostrobin was established based on effective concentration for 50% inhibition of mycelial growth (EC50) values of 153 isolates of S. sclerotiorum collected from five provinces of China and toxicity of alternative oxidase inhibitor salicylhydroxamic acid (SHAM) to S. sclerotiorum was determined. Results showed that the frequency distribution of EC50 values of the 153 isolates was unimodal but with a right-hand tail. The mean EC50 value was 0.1027 µg/ml and the range of EC50 values was 0.0124 to 0.6324 µg/ml. Applied as a preventive fungicide in pot experiments, pyraclostrobin at 5, 15, and 45 µg/ml provided control efficacies of 61, 77, and 100%, respectively. There was no positive cross-resistance between pyraclostrobin and carbendazim or dimethachlon. EC50 values for SHAM against four isolates of S. sclerotiorum were 44.4, 51.8, 54.4, and 68.7 µg/ml. SHAM at 20 µg/ml could significantly increase not only the inhibitory effect of pyraclostrobin on mycelial growth on potato dextrose agar media but also the control efficacy in planta. These results indicated that SHAM should not be added into artificial media in in vitro assay of S. sclerotiorum sensitivity to pyraclostrobin. This has broad implications for assay of sensitivity of fungal pathogen to QoI fungicides.

Dimethachlon Resistance in Sclerotinia sclerotiorum in China.

The dicarboximide fungicide dimethachlon has been widely used for controlling Sclerotinia sclerotiorum in China for more than a decade. To assess the current status of dimethachlon resistance in S. sclerotiorum in China, 2,424 isolates were collected from disease-infected oilseed rape and soybean plants in five provinces of China in 2011 and 2012, and dimethachlon resistance was monitored by mycelial growth inhibition method on potato dextrose agar (PDA) media. Dimethachlon at 5 µg/ml was used as a discriminatory dose to detect resistance in all isolates, and 50% effective concentration values were determined for all dimethachlon-resistant isolates and some sensitive isolates. No dimethachlon resistance was detected in isolates from Anhui province (eastern China), Gansu province (northwestern China), and Qinghai province (western China). In Hunan province (central China), 3 of 268 (1.12%) isolates collected from oilseed rape plants in 2012 were resistant to dimethachlon, and the resistance ratios for the three resistant isolates were 4.56, 32.70, and 105.53, respectively. In Heilongjiang province (northeastern China), 8 of 243 (3.29%) isolates collected from soybean plants in 2011 were resistant to dimethachlon, with resistance ratios of 5.57 to 94.80; 11 of 409 (2.69%) isolates collected in 2012 were resistant to dimethachlon, with resistance ratios of 3.21 to 9.69. Cross-resistance studies showed that there was positive cross-resistance between dimethachlon and iprodione, procymidone, and the N-phenyl carbamate fungicide diethofencarb. No cross-resistance was found between dimethachlon and carbendazim, tebuconazole, kresoxim-methyl, thiram, and boscalid. Compared with the sensitive isolates of S. sclerotiorum, the field-dimethachlon-resistant isolates were more sensitive to osmotic pressure, grew more slowly on PDA media, and were less pathogenic on leaves of oilseed rape.

Correlation between social factors and anxiety-depression in function dyspepsia: do relationships exist?

INTRODUCTION: Function dyspepsia (FD) may cause patients to suffer from anxiety and depression, and psychosocial disorders would have a significant effect on FD symptoms. AIM: To examine the prevalence of anxiety and depression among function dyspepsia (FD) patients and to identify social factors of anxiety-depression among FD patients. MATERIAL AND METHODS: Patients with FD, who fulfilled the Rome III criteria, were enrolled. All patients were administered a validated Chinese version of the self-rating scale (SDS) and self-rating anxiety scale (SAS), and investigated regarding the patients' social factors. RESULTS: A total of 907 patients were enrolled, including 516 (56.89%) FD patients within anxiety-depression status; SDS mean scores were 51.57 ±8.22; SAS mean scores were 51.04 ±7.53; 52.28% were male and 64.25% were female (χ(2) = 262.54, p < 0.01); 56.16% were aged 18-29 years, 54.15% were aged 30-39 years, 54.77% were aged 40-49 years, 62.02% were aged 50-59 years, 69.23% were aged above 60 years (χ(2) = 18.14, p < 0.01); 67.44% were the retirees; 63.31% were manual workers; 55.10% were soldiers; 43.57% were mental workers; 38.89% were students (χ(2) = 716.53, p < 0.01); 64.20% had junior high school degree or below; 57.36% had high school degrees; 42.03% had college degrees; 44.44% had master's or above degrees (χ(2) = 27.21, p < 0.05); 38.10% were in good health condition; 61.90% were in poor health condition (χ(2) = 7.94, p < 0.01); 20.31% had correlative family history; and 79.69% had no correlative family history (χ(2) = 2.23, p > 0.05). CONCLUSIONS: The FD patients have higher rates of anxiety and depression. Gender, age, occupation, education level, and health condition have a significant effect on anxiety and depression status. Female gender, advanced age, high-stress occupation, lower education level, and poor health condition all are risk factors. Family history has no relationship with anxiety and depression among FD patients.

[Drug sensitivity analysis of Mycobacterium chelonae and Mycobacterium abscessus and evaluation of Etest for susceptibility testing].

OBJECTIVE: To study the drug resistance profile of Mycobacterium(M.) chelonae and M.abscessus and to evaluate the clinical application of Etest(epsilometer test) for susceptibility testing. METHODS: Twenty clinical isolates of M.abscessus and 16 clinical isolates of M.chelonae from clinical specimens were collected.Strain identification was carried out by GenoType Mycobacterium CM assay(Hain Lifescience, Germany). The accuracy was evaluated by comparing Etest results to those obtained by broth microdilution. Thirty-six isolates were tested against amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, sulfamethoxazole and tobramycin. The agreement among MICs and interpretive category was evaluated. Chi-squared test was used to compare observed frequency of each of the 2 examples. RESULTS: All of the isolates(36/36) were sensitive to amikacin and cefoxitin, and only 1 isolate(1/36) was resistant to clarithromycin, but more isolates(29/36) were resistant to ciprofloxacin, doxycycline, imipenem and sulfamethoxazole.For M.chelonae, only 2/16 were resistant to linezolid, and 7/16 resistant to tobramycin.For M.abscessus, more than 12/20 were resistant to linezolid and 16/20 resistant to tobramycin. The agreement between broth microdilution MICs and Etest MICs for 9 drugs was 149/324.With amikacin, clarithromycin, doxycycline and imipenem, the agreement for interpretive category was excellent(35/36), followed by sulfamethoxazole(34/36), which corresponded to rarely very major error of 2/36.With ciprofloxacin and tobramycin, agreement for interpretive category was 31/36 and 26/36.With cefoxitin and linezolid, the agreement of Etest MICs was the lowest(14/36), resulting in the resistant category. CONCLUSIONS: Isolates of M.chelonae and M.abscessus exhibit far more susceptibility to amikacin, cefoxitin and clarithromycin than any other antimicrobial agents.Linezolid and tobramycin showed sensitivity to some isolates of M.chelonae.It is suitable for the Etest method as a simple reliable method for the drug susceptibility of amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem, and tobramycin except to cefoxitin and linezolid. The Etest method of determining sulfamethoxazole susceptibility should be careful.

Influence prediction of tissue injury on frequency variations of the lumbar spine under vibration.

A three-dimensional finite element model of the spine T12-S1 segment was developed and used to investigate biodynamics characteristics of the human lumbar spine. The T12-S1 model was carefully built including spinal vertebrae, intervertebral discs, and ligaments so as to approach the real human spine. Finite element modal analysis was carried out to obtain vibration modes and resonant frequencies of the spine. The analytical results indicate that the vertical resonant frequency of the spinal T12-S1 segment with a mass of 40 kg on the top vertebra is 7.68 Hz. The vertical resonant frequencies of spine motion segments decrease with the number of spine motion segments increasing. The tissue injury, such as disc denucleation and removal both of facet articulations and their capsular ligaments may decrease the resonant frequencies of spine in different extent. The denucleation makes larger influence on vertical resonant frequencies than facetectomy does. The denucleation is more harmful to the facet articulations under whole body vibration. The dynamic characteristics of the T12-S1 model accords with the actual human spine, and it is useful for the relative studies of the human spine, such as biomechanical characteristics, vibration-related injury mechanism of the human spine, and development of vibration-related mechanical products.

Influence of anteroposterior shifting of trunk mass centroid on vibrational configuration of human spine.

This study attempts to determine the influence of anteroposterior (A-P) shifting of trunk mass from the upright sedentary posture on dynamic characteristics of the human lumbar spine. A three-dimensional finite element (FE) model comprising of the T12-Pelvis spine unit was used to mimic the human spine system. It is not clear how the A-P shifting of the upper part of human upper body affect on vibrational modality of the human lumbar spine under whole body vibration. Five trunk mass point locations were assumed by 2.0cm anterior, 1.0cm anterior, 1.0cm posterior and 2.0cm posterior to the upright sedentary posture including no shifting posture. FE modal analysis was used to extract the resonant frequencies and vibration modes of the human spine. The analytical results indicate that trunk mass centroid shifting onwards or rearwards may result in a reduction of vertical resonant frequency of the human spine. The human spine has the highest vertical resonant frequency at the normal upright sedentary posture with the trunk mass locating around 1.0cm anterior to the L3-L4 vertebral centroid. Larger A-P deformations and rotational deformations were also found at the spine motion segments L3-L4 and L4-L5, which imply higher compressive stress and shear stress at the disc annulus of those spinal motion segments. The findings in this study may explain why long-term whole body vibration might induce the degeneration of human spine at the relevant spinal motion segments.

[Thermal dosimetric study on hyperthermia combined with radiotherapy for deep seated pelvic malignancies].

OBJECTIVE: To ascertain a clinically meaningful thermal dose unit-temperature equivalent minute (TEM) 42.5 degrees C and the relationship between TEM 42.5 degrees C and tumor response rate. METHODS: From August 1998 to December 2002, 49 patients with recurrent or metastatic malignancies in the pelvis were treated with hyperthermia combined with conventional radiotherapy. Direct thermometry with high resistance lead needle was used whenever possible to measure the temperature by inserting Teflon catheter into the tumor. TEM 42.5 degrees C was used as the thermal dose unit and the relationship between TEM 42.5 degrees C and tumor response rate was monitored. RESULTS: There was a positive correlation between response rate TEM 42.5 degrees C and the radiation dose. The tumor volume and number of heat treatment showed no influence on response. CONCLUSION: Both univariate analysis and multivariate logistic regression analysis indicate that there is a positive correlation between the response rate, TEM 42.5 degrees C and the radiation dose. TEM 42.5 degrees C may act as a useful thermal dose unit in the combination of hyperthermia and radiotherapy. To lower the incidence of complications in thermometry, direct thermometry with high resistance lead needle can be used to measure the temperature by inserting Teflon catheter into the deep-seated malignancies.