A Physical Measure for Characterizing Crossover from Integrable to Chaotic Quantum Systems.

In this paper, a quantity that describes a response of a system's eigenstates to a very small perturbation of physical relevance is studied as a measure for characterizing crossover from integrable to chaotic quantum systems. It is computed from the distribution of very small, rescaled components of perturbed eigenfunctions on the unperturbed basis. Physically, it gives a relative measure to prohibition of level transitions induced by the perturbation. Making use of this measure, numerical simulations in the so-called Lipkin-Meshkov-Glick model show in a clear way that the whole integrability-chaos transition region is divided into three subregions: a nearly integrable regime, a nearly chaotic regime, and a crossover regime.

Meteorological conditions are heterogeneous factors for COVID-19 risk in China.

Whether meteorological factors influence COVID-19 transmission is an issue of major public health concern, but available evidence remains unclear and limited for several reasons, including the use of report date which can lag date of symptom onset by a considerable period. We aimed to generate reliable and robust evidence of this relationship based on date of onset of symptoms. We evaluated important meteorological factors associated with daily COVID-19 counts and effective reproduction number (Rt) in China using a two-stage approach with overdispersed generalized additive models and random-effects meta-analysis. Spatial heterogeneity and stratified analyses by sex and age groups were quantified and potential effect modification was analyzed. Nationwide, there was no evidence that temperature and relative humidity affected COVID-19 incidence and Rt. However, there were heterogeneous impacts on COVID-19 risk across different regions. Importantly, there was a negative association between relative humidity and COVID-19 incidence in Central China: a 1% increase in relative humidity was associated with a 3.92% (95% CI, 1.98%-5.82%) decrease in daily counts. Older population appeared to be more sensitive to meteorological conditions, but there was no obvious difference between sexes. Linear relationships were found between meteorological variables and COVID-19 incidence. Sensitivity analysis confirmed the robustness of the association and the results based on report date were biased. Meteorological factors play heterogenous roles on COVID-19 transmission, increasing the possibility of seasonality and suggesting the epidemic is far from over. Considering potential climatic associations, we should maintain, not ease, current control measures and surveillance.

Identifying risk factors for chronic kidney disease stage 3 in adults with acquired solitary kidney from unilateral nephrectomy: a retrospective cohort study.

BACKGROUND: We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy. METHODS: We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. RESULTS: In total, 172 patients with ASK (110 men; median 58.0 years) were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039-1.115, p < 0.001), diabetes (OR 4.401, 95% CI 1.693-11.44, p = 0.002), hyperuricemia (OR 2.733, 95% CI 1.104-6.764, p = 0.03), a history of cardiovascular disease (CVD) (OR 5.583, 95% CI 1.884-18.068, p = 0.002), and ASK due to renal tuberculosis (OR 8.816, 95% CI 2.92-26.62, p < 0.001) were independent risk factors for developing CKD stage 3 among patients with ASK. CONCLUSIONS: Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis.

Novel, linked bioreactor system for continuous production of biologics.

A novel, alternative intensified cell culture process comprised of a linked bioreactor system is presented. An N-1 perfusion bioreactor maintained cells in a highly proliferative state and provided a continuous inoculum source to a second bioreactor operating as a continuous-flow stirred-tank reactor (CSTR). An initial study evaluated multiple system steady-states by varying N-1 steady-state viable cell densities, N-1 to CSTR working volume ratios, and CSTR dilution rates. After identifying near optimum system steady-state parameters yielding a relatively high volumetric productivity while efficiently consuming media, a subsequent lab-scale experiment demonstrated the startup and long-term operation of the envisioned manufacturing process for 83 days. Additionally, to compensate for the cell-specific productivity loss over time due to cell line instability, the N-1 culture was also replaced with younger generation cells, without disturbing the steady-state of the system. Using the model cell line, the system demonstrated a two-fold volumetric productivity increase over the commercial-ready, optimized fed-batch process.

Role of Locoregional Treatment in Vulvar Cancer With Pelvic Lymph Node Metastases: Time to Reconsider FIGO Staging?

BACKGROUND: Vulvar cancer with pelvic nodal involvement is considered metastatic (M1) disease per AJCC staging. The role of definitive therapy and its resulting impact on survival have not been defined. PATIENTS AND METHODS: Patients with pelvic lymph node-positive vulvar cancer diagnosed in 2009 through 2015 were evaluated from the National Cancer Database. Patients with known distant metastatic disease were excluded. Logistic regression was used to evaluate use of surgery and radiation therapy (RT). Overall survival (OS) was evaluated with log-rank test and Cox proportional hazards modeling (multivariate analysis [MVA]). A 2-month conditional landmark analysis was performed. RESULTS: A total of 1,304 women met the inclusion criteria. Median follow-up was 38 months for survivors. Chemotherapy, RT, and surgery were used in 54%, 74%, and 62% of patients, respectively. Surgery was associated with prolonged OS (hazard ratio [HR], 0.58; P<.001) but had multiple significant differences in baseline characteristics compared with nonsurgical patients. In patients managed nonsurgically, RT was associated with prolonged OS (HR, 0.66; P=.019) in MVA. In patients undergoing surgery, RT was associated with better OS (3-year OS, 55% vs 48%; P=.033). Factors predicting use of RT were identified. MVA revealed that RT was associated with prolonged OS (HR, 0.75; P=.004). CONCLUSIONS: In this cohort of women with vulvar cancer and positive pelvic lymph nodes, use of RT was associated with prolonged survival in those who did not undergo surgery. Surgery followed by adjuvant RT was associated with prolonged survival compared with surgery alone.

SF36 Is a Reliable Patient-Oriented Outcome Evaluation Tool in Surgically Treated Degenerative Cervical Myelopathy Cases: A Systematic Review and Meta-Analysis.

BACKGROUND Degenerative spinal disorders have adverse impacts on patients' quality of life. Because the main objectives of any surgical intervention are to improve health-related quality of life and to reduce disability, instruments capable of measuring patient-oriented outcomes are now increasingly used. The aim of this study was to evaluate the use of the Short Form 36 Health Survey Questionnaire (SF36) for assessing patient-oriented outcomes of degenerative cervical myelopathy surgery. MATERIAL AND METHODS A literature search was conducted in electronic databases (Google Scholar, Ovid SP, PubMed, Science Direct, and Springer). Studies were included if they reported SF36 scores by following patients for at least 12 months. Random effects meta-analyses were performed to estimate changes in SF36 physical/mental component summary (SF36-PCS/MCS), SF36 dimensional, Japanese Orthopedics Association (JOA)/modified JOA (mJOA), and Neck Disability Index (NDI) scores by latest follow-up. RESULTS Fourteen studies (1966 patients; age 58.2 years [95% confidence interval (CI), 56.6 to 59.9]; 60% males [95% CI, 55 to 64]; follow-up 24.8 months [95% CI, 20.9 to 28.7]) were included in meta-analysis. SF36-PCS (6.60 [95% CI, 4.91 to 8.28]; p<0.00001), SF36-MCS (6.33 [95% CI, 4.31 to 8.35]; p<0.00001) and SF36 dimensional (p<0.05) scores improved significantly at latest follow-up. Surgery significantly improved JOA/mJOA (3.43 [95% CI, 2.80 to 4.06]; p<0.00001) and NDI (-13.70 [95% CI, -17.35 to -10.06]; p<0.00001) scores also. Change in SF36-PCS score were correlated (r=-0.554) with change in NDI score, whereas change in SF36-MCS score was correlated with change in JOA score (r=0.550). CONCLUSIONS Surgery for degenerative cervical myelopathy is associated with significantly improved SF36-measured patient-oriented outcomes.

Improved survival with adjuvant brachytherapy in stage IA endometrial cancer of unfavorable histology.

PURPOSE: We evaluated the utilization of vaginal brachytherapy (BT) and the resulting impact on survival in stage IA endometrial cancer of clear cell (CC), papillary serous (PS), and carcinosarcoma (CS) histology. METHODS: Patients with uterine cancer diagnosed from 2004 to 2015 were identified from the National Cancer Database. Patients underwent hysterectomy, showing FIGO stage IA disease with CC, PS, or CS histology. Logistic regression was used to evaluate predictors of BT utilization and to generate propensity scores. Survival was compared using log-rank test and Cox proportional hazards modeling, with propensity score adjustment. RESULTS: We identified 5711 patients who underwent hysterectomy showing FIGO pT1a, N0 or NX endometrial cancer with CC, PS, or CS histology, of which 29.5% received BT. Multivariate predictors of increased receipt of BT were identified. With a median follow-up of 3.3 years, 3-year overall survival (OS) was 87% for those receiving BT versus 78% for those without (p < 0.001). A survival benefit to BT was maintained across histologies. Similar results were seen whether tumor was confined to endometrium or had <50% myometrial invasion. On multivariate analysis, receipt of BT was associated with increased survival (hazard ratio [HR] 0.75, 95% confidence interval 0.65-0.87, p < 0.001). The benefit of BT persisted after propensity score adjustment (HR 0.76, p < 0.001). CONCLUSIONS: In this cohort of women with stage IA endometrial cancer of unfavorable histology, the use of BT was associated with improved survival. In this study, 29.5% of patients in our cohort received BT.

Prognosis and treatment of non-metastatic primary and secondary breast angiosarcoma: a comparative study.

BACKGROUND: Breast angiosarcoma is a rare malignancy with limited publications confined to small retrospective case reviews and case reports. Knowledge of this disease is limited because information from previous studies is insufficient and inconsistent. METHODS: We obtained data from the Surveillance, Epidemiology, and End Results Program for non-metastatic primary and secondary breast angiosarcoma, and performed analysis to determine clinicopathological characteristics and estimate their associations with overall survival (OS). RESULTS: Median age was 50-54 years in primary breast angiosarcoma and 70-74 years in secondary breast angiosarcoma, while median OS was 93 and 32 months, respectively. Age, tumor grade and tumor spread were associated with poor survival outcomes. Compared with primary breast angiosarcoma, patients with secondary breast angiosarcoma had a "nominal" increased death risk (HR = 1.89, 95% CI, 1.43-2.50, p < 0.001), which was driven by older age and more aggressive tumor phenotype at presentation. Mastectomy was associated with worse OS compared with breast conservative surgery (BCS) (adjHR = 2.47, 95% CI, 1.29-4.74) in primary angiosarcoma patients. Adjuvant radiation was associated with worse OS in secondary angiosarcoma patients (adjHR =1.77, 95% CI, 1.01-3.12). CONCLUSIONS: There is a "nominal" increased death risk in secondary breast angiosarcoma due to advanced clinicopathological features. Both BCS and mastectomy are feasible in primary and secondary angiosarcoma if R0 can be achieved. Routine radiation in unselected breast angiosarcoma should be cautious because there is no survival benefit in primary AS and appeared to be associated with a worse OS in secondary AS.

Cell-controlled hybrid perfusion fed-batch CHO cell process provides significant productivity improvement over conventional fed-batch cultures.

A simple method originally designed to control lactate accumulation in fed-batch cultures of Chinese Hamster Ovary (CHO) cells has been modified and extended to allow cells in culture to control their own rate of perfusion to precisely deliver nutritional requirements. The method allows for very fast expansion of cells to high density while using a minimal volume of concentrated perfusion medium. When the short-duration cell-controlled perfusion is performed in the production bioreactor and is immediately followed by a conventional fed-batch culture using highly concentrated feeds, the overall productivity of the culture is approximately doubled when compared with a highly optimized state-of-the-art fed-batch process. The technology was applied with near uniform success to five CHO cell processes producing five different humanized monoclonal antibodies. The increases in productivity were due to the increases in sustained viable cell densities. Biotechnol. Bioeng. 2017;114: 1438-1447. © 2017 Wiley Periodicals, Inc.

Risk Factor Analysis for AKI Including Laboratory Indicators: a Nationwide Multicenter Study of Hospitalized Patients.

BACKGROUND/AIMS: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. METHODS: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes' definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality. RESULTS: The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set. CONCLUSION: In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI.

Effects of Traditional Chinese Medicine herbs for tonifying Qi and kidney, and replenishing spleen on intermittent asthma in children aged 2 to 5 years old.

OBJECTIVE: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) herbs for tonifying Qi and kidney, and replenishing spleen on intermittent asthma in children aged 2 and 5 years. METHODS: A randomized, single-blind, placebo controlled trial was conducted. Children with intermittent asthma were enrolled and their baseline conditions were measured using a questionnaire. A total of 60 participants, aged 2 to 5, were randomized into either the treatment group (n = 40) or the placebo group (n = 20). The treatment group was treated with granules of TCM herbs for tonifying Qi and kidney, and replenishing spleen, and the placebo group was given placebo granules for 3 months. The number of asthma attacks was counted and TCM syndrome scores were measured at 1, 2, 3, 6, 9, and 12 months. The airway resistance and levels of eosinophil cationic protein for the two groups were observed before and after 3 months. The results were statistically analyzed. RESULTS: Compared with the placebo group, the number of asthma attacks significantly decreased in the treatment group (P < 0.05). For the treatment group, the TCM syndrome scores decreased after 1 and 2 months; there was also a significant difference in scores between the two groups (P < 0.05). The difference remained after the medicine was stopped for 9 months (P < 0.05). After the 3-month treatment, compared with the placebo group, the airway resistance decreased in the treatment group (P < 0.05). No adverse events were reported in the treatment group. CONCLUSION: The TCM herbs for tonifying Qi and kidney, and replenishing spleen reduced the number of intermittent asthma attacks, decreased the TCM syndrome scores, and reduced the airway resistance in the children aged 2 to 5.

Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death.

Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-kappaB. Both Myc and the multikinase inhibitor sorafenib block NF-kappaB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.

Rating the quality of evidence: the GRADE system in systematic reviews/meta-analyses of AKI.

BACKGROUND: The method of systematic reviews/meta-analyses (SRs/MAs) has been widely used in acute kidney injury (AKI) studies. However, it is not quite clear about the quality of the evidence and existing problems. OBJECTIVES: To grade the evidence quality of published SRs/MAs of AKI by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, understand the current situation of evidence rating and analyze the possible problems. METHODS: Researchers systematically searched for articles about SRs/MAs of AKI published in the following four Chinese databases and four English databases, including Chinese Biomedicine Literature Database, Wanfang Database, China National Knowledge Internet Database, VIP Database, Pubmed, EMBASE, the Cochrane Library and Web of Science. RESULTS: Totally, 81 SRs/MAs were included in this study and the overall quality of evidence was not satisfactory. The number of literatures of low and very low evidence quality was 33 (40.7%) and 41 (50.6%), respectively. Limitation was the main factor which caused the quality of research evidence degrading (92.6%), and other degradation factors were inconsistency (56.8%), publication bias (44.4%), indirectness (35.8%) and imprecision (32.1%). The quality of evidence for AKI has been significantly improved after the publication of the GRADE system in 2004. CONCLUSIONS: Since 2004 when the GRADE system was published, the quality of evidence of AKI has been increased clearly. But quality of AKI evidence of SRs/MAs for intervention is still not satisfactory. Limitation and inconsistency were two major factors leading to degradation.

[Correlation Study on Pathological Characteristics of Target Organs and Excess Evil Syndrome in IgA Nephropathy].

OBJECTIVE: To explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy. METHODS: Data were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed. RESULTS: Four syndrome types were correlated with their Hass levels (r = 0. 341, P <0. 01). Affection of exogenous wind-heat syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters. CONCLUSIONS: Excess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.

The relationship between umbilical cord blood IL-22 level and infantile eczema at 42 days.

Background: The occurrence of eczema is related to helper T 22 (Th22) cytokine disorder, and Th22 mainly secretes interleukin-22 (IL-22). This study aims to investigate the predictive value of umbilical cord blood IL-22 levels on the onset of eczema in infants within 42 days. Study design: The study selected 157 full-term healthy neonates born between September 2020 and May 2021. Cord blood was collected immediately after birth to determine IL-22 levels, and the infants were followed up for 42 days to assess the incidence of eczema. Results: Among the 157 infants who completed the 42-day follow-up, 86 developed eczema and 71 did not. The level of IL-22 in the umbilical cord blood of the eczema group was lower than that of the non-eczema group (p < 0.05). Additionally, the incidence of eczema in children whose Family history of allergy was significantly higher than in the group without eczema (p < 0.05). Logistic regression analysis indicated that low cord blood IL-22 levels and a family history of allergies were independent risk factors for eczema (p < 0.05). The ROC curve of cord blood IL-22 levels and infant eczema showed that the cut-off value is 36.362 pg/ml, the area under the curve (AUC) is 0.613, the standard error is 0.045, the 95% CI is 0.526-0.701, the sensitivity is 63.4%, and the specificity is 57.0%. Therefore, there is a certain correlation between cord blood IL-22 levels and the incidence of infant eczema. Conclusions: Low IL-22 levels in umbilical cord blood may be linked to the development of infant eczema within 42 days, indicating a potential predictive value, although this value appears to be limited.

Comprehensive characterization of higher order structure changes in methionine oxidized monoclonal antibodies via NMR chemometric analysis and biophysical approaches.

The higher order structure (HOS) of monoclonal antibodies (mAbs) is an important quality attribute with strong contribution to clinically relevant biological functions and drug safety. Due to the multi-faceted nature of HOS, the synergy of multiple complementary analytical approaches can substantially improve the understanding, accuracy, and resolution of HOS characterization. In this study, we applied one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopy coupled with chemometric analysis, as well as circular dichroism (CD), differential scanning calorimetry (DSC), and fluorescence spectroscopy as orthogonal methods, to characterize the impact of methionine (Met) oxidation on the HOS of an IgG1 mAb. We used a forced degradation method involving concentration-dependent oxidation by peracetic acid, in which Met oxidation is site-specifically quantified by liquid chromatography-mass spectrometry. Conventional biophysical techniques report nuanced results, in which CD detects no change to the secondary structure and little change in the tertiary structure. Yet, DSC measurements show the destabilization of Fab and Fc domains due to Met oxidation. More importantly, our study demonstrates that 1D and 2D NMR and chemometric analysis can provide semi-quantitative analysis of chemical modifications and resolve localized conformational changes with high sensitivity. Furthermore, we leveraged a novel 15N-Met labeling technique of the antibody to directly observe structural perturbations at the oxidation sites. The NMR methods described here to probe HOS changes are highly reliable and practical in biopharmaceutical characterization.

Influence of the Second-Phase Resin Structure on the Interfacial Shear Strength of Carbon Fiber/Epoxy Resin.

The toughening modification of epoxy resin has received widespread attention. The addition of the second-phase resin has a good toughening effect on epoxy resin. In order to investigate the effect of the second-phase resin on the interphase of composites, in this work the interfacial properties of carbon fiber (CF)/epoxy resin with the second-phase resin structure were investigated. Methodologies including surface structure observation, chemical characteristics, surface energy of the CF, and micro-phase structure characterization of resin were tested, followed by the micro-interfacial performance of CF/epoxy composites before and after hygrothermal treatment. The results revealed that the sizing process has the positive effect of increasing the interfacial bonding properties of CF/epoxy. From the interfacial shear strength (IFSS) test, the introduction of the second phase in the resin reduced the interfacial bonding performance between the CF and epoxy. After the hygrothermal treatment, water molecules diffused along the interfacial paths between the two resins, which in turn created defects and consequently brought about a reduction in the IFSS.

Critical role for Daxx in regulating Mdm2.

The tumour suppressor p53 induces apoptosis or cell-cycle arrest in response to genotoxic and other stresses. In unstressed cells, the anti-proliferative effects of p53 are restrained by mouse double minute 2 (Mdm2), a ubiquitin ligase (E3) that promotes p53 ubiquitination and degradation. Mdm2 also mediates its own degradation through auto-ubiquitination. It is unclear how the cis- and trans-E3 activities of Mdm2, which have opposing effects on cell fate, are differentially regulated. Here, we show that death domain-associated protein (Daxx) is required for Mdm2 stability. Downregulation of Daxx decreases Mdm2 levels, whereas overexpression of Daxx strongly stabilizes Mdm2. Daxx simultaneously binds to Mdm2 and the deubiquitinase Hausp, and it mediates the stabilizing effect of Hausp on Mdm2. In addition, Daxx enhances the intrinsic E3 activity of Mdm2 towards p53. On DNA damage, Daxx dissociates from Mdm2, which correlates with Mdm2 self-degradation. These findings reveal that Daxx modulates the function of Mdm2 at multiple levels and suggest that the disruption of the Mdm2-Daxx interaction may be important for p53 activation in response to DNA damage.

Treatment of Erythrodermic Psoriasis in Children with Secukinumab: A Case Report.

Erythrodermic psoriasis (EP) is a rare and severe type of psoriasis. Common systemic therapies for children with EP include treatment with glucocorticoids, cyclosporine, acitretin, and methotrexate. Although these drugs are effective, they may cause serious side effects to children. Secukinumab has recently demonstrated efficacy in treating plaque psoriasis, but its efficacy in EP children remains unknown. We report a case of a seven-year-old patient who transitioned from generalized pustular psoriasis (GPP) to EP after routine systemic drug treatment. The patient was then treated with secukinumab. The patient's condition improved noticeably within 48 hours after the first injection. After the fifth injection, she almost completely cleared her skin lesions and achieved Psoriasis Area and Severity Index 90 (PASI 90) scores. During this period, she experienced only one respiratory infection. She completed all 11 doses of secukinumab by October 14, 2022, with no new rash (PASI 100) and no adverse drug reactions. Follow-up observation on March 15, 2023, showed no new rash (PASI 100) and no adverse reactions after medication withdrawal. This case suggests that it may also be effective in treating children with EP.

Early Warning Models for Predicting Severity in Febrile and Nonfebrile Stages of Hemorrhagic Fever with Renal Syndrome.

Treating severe hemorrhagic fever with renal syndrome (HFRS) cases is difficult. There is currently no early warning model for patients with severe HFRS. Data from 235 patients with HFRS between January 2013 and December 2019, as well as 394 laboratory indicators, were retrospectively collected. A multivariate logistic regression model was used to construct an early warning model for severe diseases. The model's accuracy was evaluated based on the area under the receiver operating characteristic curve. The area under the curve of the early warning models for both exceeded 0.9 for the two stages. In the febrile stage, there were significant differences between the severe and mild groups (P < 0.05) in renal estimated glomerular filtration rate (eGFR), urinary leukocytes, electrolytes, urine conductivity, and urinary epithelial cell count. In the nonfebrile stage, there were significant differences between the severe and mild groups (P < 0.05) in renal eGFR, electrolytes, urine conductivity, and renal cystatin C levels. The two early warning models were well-fitted and exhibited excellent predictive performance. This can help clinicians gain time to provide appropriate preemptive treatment to avoid the further development of severe disease and reduce the mortality rate.