Molecular data and morphological characters clarify the taxonomic status of Pintara heringi pieridoides (Liu & Gu, 1994) (Hesperiidae, Pyrginae).

We found Albiphasma heringi (Mell, 1922) and A. pieridoides (Liu & Gu, 1994) to be conspecific by the 658 bp COI gene sequences and male genitalia characters. Considering the distinguishable wing patterns and allopatric distribution of the two taxa, we treat pieridoides as a subspecies of heringi. Therefore, the genus Albiphasma Huang, Chiba, Wang and Fan, 2016, which was established for heringi and pieridoides, becomes monotypic, and in light of morphological similarities and close genetic distance between heringi and Pintara bowringi (Joicey & Talbot, 1921), we propose its synonymy with Pintara Evans, 1932. The adults and male genitalia of both P. heringi heringi (Mell, 1922) and P. heringi pieridoides (Liu & Gu, 1994) are illustrated.

[Overexpression of lncRNA HEM2M alleviates liver injury in mice with non-alcoholic fatty liver disease].

OBJECTIVE: To explore the effects of long non-coding RNA (lncRNA) HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease (NAFLD). METHODS: Wild-type C57BL/6 (WT) mice and myeloid cell-specific HEM2M knock-in (MYKI) mice were fed normal (ND) or high-fat diet (HFD) for 12 weeks. After intraperitoneal glucose tolerance and insulin tolerance tests, the mice were euthanized for detection of liver function indicators in the serum and liver tissue. HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies, and the levels of IL-6, IL-1ß, and TNF-α in the liver tissues were determined with ELISA. The mRNA expressions of HEM2M and the markers of M1 macrophages (TNF-α, iNOS, and IL-6) and M2 macrophages (Arg-1, YM-1, and IL-10) were detected using qRT-PCR, and the protein expressions of P-AKT, T-AKT, NLRC4, caspase-1 and GSDMD were assayed using immunoblotting. Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay. RESULTS: Compared with HFD-fed WT mice, MYKI mice with HFD feeding showed milder liver function damage (P < 0.01), alleviated hepatic steatosis, and reduced liver macrophage infiltration, glucose tolerance impairment and insulin resistance (P < 0.01). The levels of IL-6, IL-1ß, and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased (P < 0.01) and those of M2 type markers increased (P < 0.01) in the liver tissues of HFD-fed MYKI mice, which also showed reduced NLRC4 inflammasome activity, caspase-1 activation, and GSDMD-N protein expression compared with their WT counterparts (P < 0.05). CONCLUSION: Overexpression of HEM2M reduces the production of hepatic inflammatory factors, improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation, which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[The consistency of skeletal muscle mass measured by CT at L1 and L3 levels and the correlation of skeletal muscle density at L1 level with prognosis in dialysis patients].

Objective: To investigate the consistency of skeletal muscle mass by CT at 1st lumbar vertebrae (L1) and 3rd lumbar vertebrae (L3) levels and the correlation of skeletal muscle density (SMD) at L1 level with prognosis in dialysis patients. Methods: A total of 1 020 patients who underwent initial dialysis and had CT examination data in four centers (Zhongda Hospital Affiliated to Southeast University, the Third Affiliated Hospital of Soochow University, Taizhou People's Hospital Affiliated to Nanjing Medical University and the Affiliated Hospital of Yangzhou University) from January 2014 to December 2019 were retrospectively collected. The skeletal muscle index (SMI) and SMD at L1 and L3 CT images were measured and calculated in patients with both L1 and L3 level CT images. The consistency of SMI and SMD at L1 and L3 levels was analyzed, and the cut-off value of SMI and SMD at L1 level for predicting all-cause mortality and their correlation with the prognosis of dialysis patients were studied. Cox regression model was used to analyze the risk factors for all-cause death and cardiac death. Results: A total of 383 patients had both L1 and L3 level images, including 233 males and 150 females. The average SMD value of 16 samples (4.2%) exceeded the 95% consistency limit range (-8.71 to 7.75 HU), and the average SMI value of 15 samples (3.9%) exceeded the 95% consistency limit range (-20.45 to 9.53 HU). The optimal cut-off value of SMD at L1 level for predicting all-cause mortality was 36.46 HU and the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.658 (95%CI: 0.596-0.721, P<0.001), with the sensitivity and specificity of 83.8% and 57.5%, respectively. SMI at L1 level was not significantly associated with all-cause mortality (P=0.299). Multivariate Cox regression analysis showed that low SMD at L1 level was associated with all-cause mortality (HR=2.861, 95%CI: 1.576-5.193, P=0.001) and cardiac death (HR=3.771, 95%CI:1.462-9.724, P=0.006). Conclusions: SMD at L1 levelis consistent with SMD at L3 level and can be used to evaluate muscle mass. Low SMD is a risk factor for mortality in dialysis patients.

[Early results of modified Bikini approach periacetabular osteotomy for the treatment of developmental hip dysplasia under 50 years of age].

Objective: To investigate the efficacy and safety of modified Bikini approach periacetabular osteotomy in the treatment of developmental hip dysplasia under 50 years of age. Methods: The clinical data of 39 patients with developmental hip dysplasia who underwent periacetabular osteotomy in the Department of Orthopedics, Guizhou Provincial People's Hospital from June 2016 to June 2021 were retrospectively analyzed.Among them, 20 patients (21 hips) underwent the improved Bikini approach (study group) and 19 patients (20 hips) underwent the improved Smith-Petersen approach (control group).In the study group, there were 3 males and 17 females, aged(M(IQR))27.5 (14.3) years (range:11 to 44 years).In the control group, there were 2 males and 17 females, aged 27.5 (19.3) years (range:17 to 47 years).Both groups were sutured in the same manner by the same physician.Incision length, operation time, intraoperative blood loss and complications were recorded.X-ray images, anterior central marginal angle (ACE), lateral central marginal Angle (LCE) and acetabulum tilt angle (Tonnis AI) were measured before and after the operation.The coverage rate of acetabulum to femoral head (AHI) was measured and calculated, and the healing time was observed.Harris Hip score, International Hip score (IHOT)-12 and visual analogue scale (VAS) were recorded before and after surgery.Vancouver Scar Scale (VSS) score and patient and observer scar assessment scale (POSAS) score were recorded 12 months after surgery.The independent sample t test,Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All patients successfully completed the operation.There was no significant difference in operation time and intraoperative blood loss between the two groups (all P>0.05).The incision length of the study group was smaller than that of the control group, and the difference was statistically significant (10.5(5.0)cm vs.15.0(3.0),W=309.000,P=0.007).Patients were followed up for (19.1±11.1) months (range:12 to 60 months).Femoral nerve stretching injury occurred in 2 cases and sciatic branch fracture occurred in 1 case in the study group, all of which recovered to normal at 3 months follow-up, while no corresponding injury occurred in the control group.Lateral femoral cutaneous nerve injury occurred in 3 cases in the study group and 2 cases in the control group.Delayed wound healing occurred in 1 case in each of the two groups, and both healed after re-operation debridement and suture.Pubic branch nonunion occurred in 4 patients in the study group and 5 patients in the control group.There were no serious complications such as sciatic nerve and femoral blood vessel injury between the 2 groups, and there was no statistical significance in the incidence of complications between the 2 groups (52.4%(11/21)vs.40.0%(8/20),χ2=0.631,P=0.427).The clinical healing time of the patient was (4.5±1.3) months after surgery (range:3.0 to 8.0 months).There were no significant differences in ACE, LCE, Tonnis AI and AHI between the 2 groups (all P>0.05).At the last follow-up, there were no significant differences in VAS,Harris hip score and IHOT-12 score between the two groups (all P>0.05).The incision scars in the study group were smaller than those in the control group, and the differences in VSS and POSAS were statistically significant (all P<0.05). Conclusion: Compared with the improved Smith-Petersen approach, the improved Bikini approach has the same early clinical efficacy in the treatment of patients with developmental hip dysplasia under the age of 50, and has the advantages of smaller postoperative incision scars, more hidden and beautiful incision, and no serious complications, which is worthy of further study and promotion.

[Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China].

Objectives: This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) . Methods: From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy. Results: The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients. Conclusion: Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Stabilizing Supersaturation with Extreme Grain Refinement in Spinodal Aluminum Alloys.

Supersaturated solid solutions can be formed in alloys from various non-equilibrium processes, but stabilizing the metastable phases against decomposition is challenging, particularly the spinodal decomposition that occurs via chemical fluctuations without energy barriers to nucleation. In this work, it is found that spinodal decomposition in supersaturated Al(Zn) solid solutions can be inhibited with straining-induced extreme grain refinement. For the refined supersaturated grains at the nanoscale, their spinodal decomposition is obviously resisted by the relaxed grain boundaries and reduced lattice defects. As grains are refined below 10 nm the decomposition is completely inhibited, in which atomic diffusion is blocked by the stable Schwarz crystal structure with vacancy-free grains. Extreme grain refinement offers a general approach to stabilize supersaturated phases with broadened compositional windows for property modulation of alloys.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

The impact of acute-phase reaction on mortality and re-fracture after zoledronic acid in hospitalized elderly osteoporotic fracture patients.

This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not. INTRODUCTION: Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery. METHODS: This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account. RESULTS: In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio [HR] 1.97 (95% CI, 1.09-3.56; P-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11-0.70; P-value = 0.007). CONCLUSIONS: Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.

[Lysosomal membrane protein Sidt2 knockout induces apoptosis of human hepatocytes in vitro independent of the autophagy-lysosomal pathway].

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 µmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells. CONCLUSION: Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.

[M2 macrophage-derived exosomal lncRNA NR_028113.1 promotes macrophage polarization possibly by activating the JAK2/STAT3 signaling pathway].

OBJECTIVE: To explore the effect of M2 macrophage-derived exosomal lncRNA NR_028113.1 on macrophage polarization and its possible mechanism. METHODS: Bone marrow-derived macrophages (BMDMs) from BALB/c mice were isolated and cultured in vitro. After IL-4 treatment to induce M2 macrophage polarization, exosomes (M2-exo) were extracted from the supernatant of M2 macrophages and identified. The expression of lncRNA in M2-exo was detected by qRT-PCR. BMDMs were co-cultured with M2-exo (100 µg/mL) or PBS for 48 h, and the changes in cellular expression levels of Arg1, YM-1, FIZZ1, iNOS and TNF-α were detected using qRT-PCR and Western blotting. The percentage of CD206+ cells was analyzed using flow cytometry, and the phosphorylation levels of JAK2/STAT3 proteins were detected using Western blotting. A lncRNA smart silencer was designed to specifically inhibit the expression of lncRNA NR_028113.1 in the M2 macrophages, from which exosomes were extracted and co-cultured with BMDMs for 48 h. The mRNA expression levels of Arg1, YM-1, FIZZ1, iNOS and TNF-α, CD206+ cell percentage and the phosphorylation levels of JAK2/STAT3 proteins were detected using qRT-PCR, flow cytometry and Western blotting. RESULTS: LncRNA NR_028113.1 was highly expressed in the exosomes of M2 macrophages (P < 0.05). Co-culture with M2-exo significantly increased mRNA expressions of M2 macrophage marker genes Arg1, YM-1 and FIZZ1 (P < 0.05), lowered the expressions of iNOS and TNF-α (P < 0.05), and increased CD206+ cell percentage and JAK2/STAT3 protein phosphorylation level in BMDMs (P < 0.05). After inhibiting the expression of lncRNA NR_028113.1 in M2 macrophages, the extracted M2-exo caused significant down-regulation of the mRNA expressions of Arg1, YM-1 and FIZZ1 and up-regulation of iNOS and TNF-α mRNA (P < 0.05), resulting also in signi-ficantly reduced CD206+ cell percentage and lowered phosphorylation levels of JAK2/STAT3 proteins in co-cultured BMDM (P < 0.05). CONCLUSIONS: M2 macrophage-derived exosomal lncRNA NR_028113.1 can significantly promote M2 polarization of macrophages possibly by activating the JAK2/STAT3 signaling pathway.

[Occupational exposure level and requirements for radiation protection of nuclear medical staff].

With the rapid development of nuclear medicine, the number of nuclear medical staff has increased a lot in the past few years in China. Close-range operations, such as preparation and injections of radiopharmaceuticals, are usually carried out in nuclear medicine department. And the use of unsealed radionuclides may also create internal exposure risk. So, occupational exposure of nuclear medical staff is a main issue of occupational health management in China. In this paper, the occupational exposure level and requirements for radiation protection of nuclear medical staff are introduced to provide references for the related work that radiological health technical institutions carry out.

Inhibiting creep in nanograined alloys with stable grain boundary networks.

Creep, the time-dependent deformation of materials stressed below the yield strength, is responsible for a great number of component failures at high temperatures. Because grain boundaries (GBs) in materials usually facilitate diffusional processes in creep, eliminating GBs is a primary approach to resisting high-temperature creep in metals, such as in single-crystal superalloy turbo blades. We report a different strategy to inhibiting creep by use of stable GB networks. Plastic deformation triggered structural relaxation of high-density GBs in nanograined single-phased nickel-cobalt-chromium alloys, forming networks of stable GBs interlocked with abundant twin boundaries. The stable GB networks effectively inhibit diffusional creep processes at high temperatures. We obtained an unprecedented creep resistance, with creep rates of ~10-7 per second under gigapascal stress at 700°C (~61% melting point), outperforming that of conventional superalloys.

[Association analysis between genetic variants of matrix metalloproteinase enzyme 2 gene and the blood pressure of children and adolescents].

Objective: To explore the association between genetic variants of matrix metalloproteinase enzyme 2 (MMP2) gene and the blood pressure of children and adolescents. Methods: This cross-sectional study was performed in 2016 and included 4 155 children and adolescents in the urban area of Guangzhou. Physical examinations (including body height, weight, and blood pressure), questionnaires (including general characteristics, physical exercise, parental educational level, household income, etc.), and blood sampling were performed. Multivariable linear regression models were used to investigate the associations of MMP2 genetic variations (rs243865, rs7201) and the genetic risk score (GRS) level with standardized blood pressure. Mediating effect of standardized body mass index (BMI) was further assessed by process analysis in the association between GRS level and blood pressure, and potential additive interaction between physical activity and GRS level was analyzed using the product term in the regression model. Results: A total of 4 155 primary and secondary schoolchildren were finally included in the analysis, consisting of 1 401 (33.7%) second grade pupils of primary school, 1 422 (34.2%) first grade pupils of middle school, and 1 332 (32.1%) first-grade students of senior high school. After adjusting for age, sex, parental educational level, and family income, as compared to the rs243865 TT genotype, the CC/CT genotype increased diastolic blood pressure (DBP) by 0.461 standard deviations (SD) (ß for dominant model=0.461, 95%CI 0.199-0.723). When compared to the rs7201 CC genotype, the AA/AC genotype showed 0.147 SD higher systolic blood pressure (SBP) (ß for recessive model=0.147, 95%CI 0.014-0.279) and 0.171 SD increased DBP (ß for recessive model=0.171, 95%CI 0.039-0.304). For each increment of GRS level, SBP and DBP increased by 0.151 SD (ß for dominant model=0.151, 95%CI 0.029-0.272) and 0.242 SD (ß=0.242, 95%CI 0.120-0.363), respectively. The mediating effect of BMI accounted for 28.3% and 12.6% of the total effect of GRS on SBP and DBP, respectively. After controlling BMI, the direct effect of GRS on DBP remained statistically significant (P<0.001). The insufficient moderate-to-vigorous physical activity (<0.5 h/d) showed a significant interaction with GRS on SBP under additive scale (ß for interaction=0.518, 95%CI 0.088-0.949, P=0.018). Conclusions: rs243865 and rs7201 variants in MMP2 gene are associated with the elevated blood pressure of children and adolescents. Obesity may yield a mediation role in the associations, while insufficient physical activity may have a positively additive interaction with MMP2 genetic variants.

Experimental Evidence of Intrinsic Current Generation by Turbulence in Stationary Tokamak Plasmas.

High-ß_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-ß_{θe} regime.

Real-world circulating tumor DNA analysis depicts resistance mechanism and clonal evolution in ALK inhibitor-treated lung adenocarcinoma patients.

BACKGROUND: Sequential treatment with different generations of anaplastic lymphoma kinase (ALK) inhibitors have been widely applied to ALK-positive lung cancer; however, resistance mutations inevitably developed. Further characterization of ALK resistance mutations may provide key guidance to subsequent therapies. Here we explored the emergence of secondary ALK mutations during sequential ALK tyrosine kinase inhibitor (TKI) treatment in a real-world study of Chinese lung adenocarcinoma (ADC) patients. METHODS: A clinical-genomic database was queried for lung ADC patients with at least one ALK inhibitor treatment and at least one plasma sample collected following ALK inhibitor treatment. Targeted genome profiling was performed with a 139-gene panel in baseline tumor tissue and serial plasma samples of patients. RESULTS: A total of 116 patients met inclusion criteria. ALK G1202R was more common in patients with echinoderm microtubule-associated protein-like 4 (EML4)-ALK v3 fusion, whereas ALK L1196M was more common in v1. TP53 mutant patients were significantly associated with harboring multiple ALK resistance mutations (P = 0.03) and v3+/TP53 mutant patients had the highest rate of multiple ALK resistance mutations. The sequential use of ALK TKI led to an increased incidence of concurrent ALK mutations along the lines of therapies. Alectinib had a lower rate (9%) harboring ALK resistance mutation as first-line ALK TKI compared with crizotinib (36%). ALK compound mutations identified included ALK D1203N/L1196M, ALK G1202R/L1196M, and ALK G1202R/F1174C, which may be lorlatinib resistant. Using paired pretreatment and post-treatment samples, we identified several ALK-independent resistance-related genetic alterations, including PTPRD and CNKN2A/B loss, MYC, MYCN and KRAS amplification, and EGFR19del. CONCLUSIONS: Sequential postprogression plasma profiling revealed that increased lines of ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance, which may provide guidance for clinical decision making.

The effect of favipiravir versus hydroxychloroquine on clinical and laboratory findings in COVID-19 in healthcare workers

Abstract Objectives Comparative data on hydroxychloroquine and favipiravir, commonly used agents in the treatment of Coronavirus Disease-2019 (COVID-19), are still limited. In this study, it was aimed to compare treatment outcomes in healthcare workers with COVID-19 who were prospectively followed by the occupational health and safety unit. Methods A total of 237 healthcare-workers, diagnosed as mild or moderate COVID-19 between March 11, 2020 and January 1, 2021, were given hydroxychloroquine (n = 114) or favipiravir (n = 123). Clinical and laboratory findings were evaluated. Results The mean age of the patients was 33.4±11.5 years. The mean time to negative PCR was found to be significantly shorter in patients receiving favipiravir compared to the hydroxychloroquine group (10.9 vs. 13.9 days; p < 0.001). The rate of hospitalization in the hydroxychloroquine group was significantly higher than favipiravir group (15.8% vs. 3.3%). In terms of side effects; the frequency of diarrhea in patients receiving hydroxychloroquine was significantly higher than that in the favipiravir group (31.6% vs. 6.5%; p < 0.001). Conclusions Favipiravir and hydroxychloroquine were similar in terms of improvement of clinical symptoms of healthcare workers with mild or moderate COVID-19 infection, but favipiravir was significantly more effective in reducing viral load and hospitalization rates. Furthermore, favipiravir caused significantly less side-effects than hydroxychloroquine.