Severe and continuous immunoparesis during induction or maintenance therapy in nontransplant patients with multiple myeloma is a sign of poor prognosis.

OBJECTIVE: Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited. METHODS: In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis. RESULTS: Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses. CONCLUSION: The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.

Research on collaborative edge network service migration strategy based on crowd clustering.

The innovative application of Crowd Intelligent Devices (CIDS) in edge networks has garnered attention due to the rapid development of artificial intelligence and computer technology. This application offers users more reliable and low-latency computing services through computation offloading technology. However, the dynamic nature of network terminals and the limited coverage of edge servers pose challenges, such as data loss and service interruption. Furthermore, the high-speed mobility of intelligent terminals in the dynamic edge network environment further complicates the design of computation offloading and service migration strategies. To address these challenges, this paper explores the computation offloading model of cluster intelligence collaboration in a heterogeneous network environment. This model involves multiple intelligences collaborating to provide computation offloading services for terminals. To accommodate various roles, a switching strategy of split-cluster group collaboration is introduced, assigning the cluster head, the alternate cluster head, and the ordinary user are assigned to a group with different functions. Additionally, the paper formulates the optimal offloading strategy for group smart terminals as a Markov decision process, taking into account factors such as user mobility, service delay, service accuracy, and migration cost. To implement this strategy, the paper utilizes the deep reinforcement learning-based CCSMS algorithm. Simulation results demonstrate that the proposed edge network service migration strategy, rooted in groupwise cluster collaboration, effectively mitigates interruption delay and enhances service migration efficiency.

Pose-Aware 3D Talking Face Synthesis using Geometry-guided Audio-Vertices Attention.

Most of the existing 3D talking face synthesis methods suffer from the lack of detailed facial expressions and realistic head poses, resulting in unsatisfactory experiences for users. In this paper, we propose a novel pose-aware 3D talking face synthesis method with a novel geometry-guided audio-vertices attention. To capture more detailed expression, such as the subtle nuances of mouth shape and eye movement, we propose to build hierarchical audio features including a global attribute feature and a series of vertex-wise local latent movement features. Then, in order to fully exploit the topology of facial models, we further propose a novel geometry-guided audio-vertices attention module to predict the displacement of each vertex by using vertex connectivity relations to take full advantage of the corresponding hierarchical audio features. Finally, to accomplish pose-aware animation, we expand the existing database with an additional pose attribute, and a novel pose estimation module is proposed by paying attention to the whole head model. Numerical experiments demonstrate the effectiveness of the proposed method on realistic expression and head movements against state-of-the-art methods.

Successful treatment pure red cell aplasia after ABO major mismatched allogeneic hematopoietic stem cell transplantation with avatrombopag and low dose rituximab.

BACKGROUND: Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with ABO major incompatibility is characterized by transfusion dependent anemia. No standard treatment existed for PRCA following allo-HSCT yet. STUDY DESIGN AND METHODS: We conducted a retrospective study, and reported our experience with the use of avatrombopag and lower dose rituximab to treat five patients with PRCA subsequent to major ABO-incompatible allo-HSCT. RESULTS: Five cases of PRCA were identified from 72 patients who underwent allo-HSCT with major or bidirectional ABO mismatch. Cumulative incidence at Day +60 was 6.9% (5/72) at our center. All donor and recipient blood groups were A+  and O+ , respectively. In the first three cases we reported, patients received erythropoietin, plasma exchange, and donor lymphocyte infusion, but none of them had any effect. After 4 weeks of treatment with low dose rituximab (100 mg/week) combined with avatrombopag (40 mg/day), favorable outcomes were obtained. According to the aforementioned experience, Cases 4 and 5 were administered low-dose rituximab and avatrombopag in 3 months after transplantation, and erythroid response was observed on 3 weeks after treatment. Our patients tolerated low-dose rituximab and avatrombopag well and experienced rapid efficacy, with a median duration of 3 weeks. Furthermore, no severe infection or thrombocytosis necessitated a dose adjustment. CONCLUSION: Low-dose rituximab and avatrombopag may be an effective treatment for patients with PRCA after major ABO-incompatible allo-HSCT. The patients should be treated at least 90 days post transplantation if conventional erythropoietin therapy fails.

Identifying sensors-based parameters associated with fall risk in community-dwelling older adults: an investigation and interpretation of discriminatory parameters.

BACKGROUND: Falls pose a severe threat to the health of older adults worldwide. Determining gait and kinematic parameters that are related to an increased risk of falls is essential for developing effective intervention and fall prevention strategies. This study aimed to investigate the discriminatory parameter, which lay an important basis for developing effective clinical screening tools for identifying high-fall-risk older adults. METHODS: Forty-one individuals aged 65 years and above living in the community participated in this study. The older adults were classified as high-fall-risk and low-fall-risk individuals based on their BBS scores. The participants wore an inertial measurement unit (IMU) while conducting the Timed Up and Go (TUG) test. Simultaneously, a depth camera acquired images of the participants' movements during the experiment. After segmenting the data according to subtasks, 142 parameters were extracted from the sensor-based data. A t-test or Mann-Whitney U test was performed on the parameters for distinguishing older adults at high risk of falling. The logistic regression was used to further quantify the role of different parameters in identifying high-fall-risk individuals. Furthermore, we conducted an ablation experiment to explore the complementary information offered by the two sensors. RESULTS: Fifteen participants were defined as high-fall-risk individuals, while twenty-six were defined as low-fall-risk individuals. 17 parameters were tested for significance with p-values less than 0.05. Some of these parameters, such as the usage of walking assistance, maximum angular velocity around the yaw axis during turn-to-sit, and step length, exhibit the greatest discriminatory abilities in identifying high-fall-risk individuals. Additionally, combining features from both devices for fall risk assessment resulted in a higher AUC of 0.882 compared to using each device separately. CONCLUSIONS: Utilizing different types of sensors can offer more comprehensive information. Interpreting parameters to physiology provides deeper insights into the identification of high-fall-risk individuals. High-fall-risk individuals typically exhibited a cautious gait, such as larger step width and shorter step length during walking. Besides, we identified some abnormal gait patterns of high-fall-risk individuals compared to low-fall-risk individuals, such as less knee flexion and a tendency to tilt the pelvis forward during turning.

Sample Size Requirements of a Pharmaceutical Material Library: A Case in Predicting Direct Compression Tablet Tensile Strength by Latent Variable Modeling.

The material library is an emerging, new data-driven approach for developing pharmaceutical process models. How many materials or samples should be involved in a particular application scenario is unclear, and the impact of sample size on process modeling is worth discussing. In this work, the direct compression process was taken as the research object, and the effects of different sample sizes of material libraries on partial least squares (PLS) modeling in the prediction of tablet tensile strength were investigated. A primary material library comprising 45 materials was built. Then, material subsets containing 5 × i (i = 1, 2, 3, …, 8) materials were sampled from the primary material library. Each subset underwent sampling 1000 times to analyze variations in model fitting performance. Both hierarchical sampling and random sampling were employed and compared, with hierarchical sampling implemented with the help of the tabletability classification index d. For each subset, modeling data were organized, incorporating 18 physical properties and tableting pressure as the independent variables and tablet tensile strength as the dependent variable. A series of chemometric indicators was used to assess model performance and find important materials for model training. It was found that the minimum R2 and RMSE values reached their maximum, and the corresponding values were kept almost unchanged when the sample sizes varied from 20 to 45. When the sample size was smaller than 15, the hierarchical sampling method was more reliable in avoiding low-quality few-shot PLS models than the random sampling method. Two important materials were identified as useful for building an initial material library. Overall, this work demonstrated that as the number of materials increased, the model's reliability improved. It also highlighted the potential for effective few-shot modeling on a small material library by controlling its information richness.

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study.

Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We conducted this study to compare the superiority of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 176 patients. In the pre-DLI cohort, 42 patients relapsed without chance for pre-DLI while 95 patients remained CR without detectable minimal residual disease (MRD). Thirty-nine patients in the pre-DLI cohort became minimal MRD positive/mixed chimerism and received pre-DLI. Pro-DLI cohort had higher 3-year progression-free-survival (PFS) (63.4%vs.53.0%, P = 0.026) and overall survival (OS) (65.2% vs. 57.0%, P = 0.14) compared to the pre-DLI cohort. The 3-year cumulative incidence of relapse (CIR) was 25.3% in the pro-DLI cohort which was significantly lower than 36.7% in the pre-DLI cohort (P = 0.02). The cumulative incidence of grade III-IV aGVHD, cGVHD and non-relapse mortality were comparable between cohorts. Multivariable analysis demonstrated strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.63, P = 0.04), PFS (HR = 0.54, P = 0.005) and CIR (HR = 0.50, P = 0.005). In high-risk patients with acute leukemia, early scheduled pro-DLI rather than pre-DLI after detectable MRD would reduce post-transplant relapse and improve long-term survival.

Analysis of transjugular intrahepatic portosystemic shunt by hemodynamic simulation.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS), which artificially creates a portocaval shunt to reduce portal venous pressure, has gradually become the primary treatment for portal hypertension (PH). However, there is no prefect shunting scheme in TIPS to balance the occurrence of postoperative complications and effective haemostasis. OBJECTIVE: To construct cirrhotic PH models and compare different shunting schemes in TIPS. METHODS: Three cases of cirrhotic PH with different liver volumes were selected for enhanced computed tomography scanning. The models for different shunting schemes were created using Mimics software, and following FLUENT calculation, all the models were imported into the software computational fluid dynamic-post for processing. In each shunting scheme, the differences in portal vein pressure, hepatic blood perfusion and blood flow from the superior mesenteric vein in the shunt tract were compared. The coefficient G was adapted to evaluate the advantages and disadvantages. RESULTS: (1) Concerning the precise location of the shunt tract, the wider the diameter of the shunt tract, the lower the pressure of the portal vein and the lesser the hepatic blood perfusion. Meanwhile, the pressure drop objective was not achieved with the 6 mm-diameter shunting scheme. (2) The 8 mm-diameter shunting scheme through the left portal vein (LPV) had the highest coefficient G. CONCLUSION: The 8 mm-diameter shunting scheme through the LPV may demonstrate a superior effect and prognosis in TIPS procedures.

The Proportion of Myeloid-derived Suppressor Cells in the Graft as a Potential Predictor of Acute Graft-versus-host Disease in Haploid Allogeneic Hematopoietic Stem Cell Transplantation.

Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD.

Efficacy and Safety of Sharp Recanalization with the Stiff End of a Microguidewire for Treatment of Refractory Central Venous Occlusions in Hemodialysis Patients.

BACKGROUND: Sharp recanalization is a viable procedure for some refractory central venous occlusions that cannot be recanalized with the conventional technique. The sharp recanalization procedures reported in previous studies are often rely on costly devices and with a certain proportion of complications. This study aimed to present an inexpensive and risk-controllable coaxial centrifugally sharp recanalization technique that was independent of any additional costly devices. METHODS: This retrospective study enrolled 8 patients who had received sharp recanalization of central venous occlusions, between August 2017 and May 2021. The sharp recanalization technique was performed centrifugally with the stiff end of a microguidewire after the lesions failed to be passed through with the conventional technique. Clinical data of patients on their lesions, technical success rate, procedure-related complications, and patency rates were collected and analyzed to assess the efficacy and safety of the technique. RESULTS: Technical success was achieved in all patients, with no complications were observed. All symptoms were ameliorated within 48h postsurgery. The median follow-up period was 22 months. All patients maintained patency or assisted patency at 12 month follow-up. CONCLUSIONS: Sharp recanalization performed centrifugally with the stiff end of the microguidewire could be a cost-effective and safe alternative procedure for the treatment of refractory central venous occlusion that cannot be recanalized with conventional technique.

Heteroepitaxial Growth of Black Phosphorus on Tin Monosulfide.

Black phosphorus (Black P), a layered semiconductor with a layer-dependent bandgap and high carrier mobility, is a promising candidate for next-generation electronics and optoelectronics. However, the synthesis of large-area, layer-precise, single crystalline Black P films remains a challenge due to their high nucleation energy. Here, we report the molecular beam heteroepitaxy of single crystalline Black P films on a tin monosulfide (SnS) buffer layer grown on Au(100). The layer-by-layer growth mode enables the preparation of monolayer to trilayer films, with band gaps that reflect layer-dependent quantum confinement.

Investigating the therapeutic potential of sinomenine in rheumatoid arthritis: anti-inflammatory, antioxidant, and immunomodulatory mechanisms.

An autoimmune disease, rheumatoid arthritis (RA) is characterized by the onset of inflammation and subsequent damage to the joints. Although several therapies are available for RA, none are effective, and many have undesirable side effects. The roots of Sinomenium acutum produce an alkaloid called Sinomenine (SIN), which has been used for centuries in Chinese medicine to treat arthritis due to its anti-inflammatory properties. This study aimed to explore the potential therapeutic benefits of SIN through oral administration following RA induction using Freund's complete adjuvant (FCA) injections. The study monitored changes in the arthritic index, hind paw volume, inflammation and oxidative stress markers. Results demonstrated that SIN effectively inhibited the activity of NF-κB and IKKß in knee joint tissues, which led to a decrease in tissue levels of TNF-α, IL-6, IL-1ß, and iNOS in RA-induced rats. The production of anti-inflammatory cytokines such as IL-10, Arg-1, and Fizz1 also increased. In rat knee joints, SIN elevated the expression of TIMP-1 and TIMP-3 and decreased the expression of MMP-2 and MMP-9. Additionally, SIN modulated the RANK/RANKL/OPG pathway in RA-induced rat knee joint tissues, reducing RANKL expression and increasing OPG. SIN also effectively decreased MDA, NO, and elevated antioxidant enzymes (SOD, CAT, GPx, and GSH) in RA-induced rats via Nrf2/Keap 1 signaling pathway activation. In conclusion, this study suggests that SIN possesses potential therapeutic benefits for treating RA by modulating the RANK/RANKL/OPG pathway, which may impact osteoclast activity, oxidative stress, and inflammation in knee joint tissues.

Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.

BACKGROUND: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. METHODS: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. RESULTS: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. CONCLUSION: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

Effectiveness of single-dose 6 mg pegfilgrastim in mobilizing peripheral blood stem cells in allogeneic hematopoietic cell transplantation donors.

A single injection of 12 mg pegfilgrastim was used to mobilize peripheral blood progenitor cells (PBPCs) from healthy donors in some studies. The purpose of this study was to determine if 6 mg of pegfilgrastim was effective and safe for mobilizing CD34+ cells in donors for allogeneic hematopoietic stem cell transplantation. We conducted a retrospective case-matched design. A single dosage of 6 mg pegfilgrastim was used to mobilize PBPCs from 60 healthy donors. Granulocyte colony-stimulating factor (G-CSF, 10 µg/kg) was administered daily to the matched donors. Leukapheresis was scheduled to commence on day 4 of the mobilization regimen. The median yielded CD34+ cell in the pegfilgrastim group was higher than those in the G-CSF group, at 5.06 × 106/kg recipient weight. The 73.3% of donors mobilized with pegfilgrastim yielded >4 × 106 cells/kg CD34+ cells in a single apheresis procedure when compared to the 33.3% of donors mobilized with G-CSF (P < 0.001). The myeloid-derived suppressor cells (MDSC) proportion in the pegfilgrastim group was significantly higher than that in the G-CSF group (P < 0.001). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was higher in the G-CSF group than that in the pegfilgrastim group (26.7% vs. 11.7%), without statistical difference. In comparison to the G-CSF group, the pegfilgrastim group had a reduced median pain intensity numerical rating scale score (1 vs. 2). A single 6 mg dosage of pegfilgrastim is effective and safe for allogeneic PBPCs collection from healthy donors. Pegfilgrastim may decrease the incidence of aGVHD by boosting MDSCs, which need further investigation.

Children's Pain Identification Based on Skin Potential Signal.

Pain management is a crucial concern in medicine, particularly in the case of children who may struggle to effectively communicate their pain. Despite the longstanding reliance on various assessment scales by medical professionals, these tools have shown limitations and subjectivity. In this paper, we present a pain assessment scheme based on skin potential signals, aiming to convert subjective pain into objective indicators for pain identification using machine learning methods. We have designed and implemented a portable non-invasive measurement device to measure skin potential signals and conducted experiments involving 623 subjects. From the experimental data, we selected 358 valid records, which were then divided into 218 silent samples and 262 pain samples. A total of 38 features were extracted from each sample, with seven features displaying superior performance in pain identification. Employing three classification algorithms, we found that the random forest algorithm achieved the highest accuracy, reaching 70.63%. While this identification rate shows promise for clinical applications, it is important to note that our results differ from state-of-the-art research, which achieved a recognition rate of 81.5%. This discrepancy arises from the fact that our pain stimuli were induced by clinical operations, making it challenging to precisely control the stimulus intensity when compared to electrical or thermal stimuli. Despite this limitation, our pain assessment scheme demonstrates significant potential in providing objective pain identification in clinical settings. Further research and refinement of the proposed approach may lead to even more accurate and reliable pain management techniques in the future.

A tabletability change classification system in supporting the tablet formulation design via the roll compaction and dry granulation process.

In this paper, the material library approach was used to uncover the pattern of tabletability change and related risk for tablet formulation design under the roll compaction and dry granulation (RCDG) process. 31 materials were fully characterized using 18 physical parameters and 9 compression behavior classification system (CBCS) parameters. Then, each material was dry granulated and sieved into small granules (125-250 µm) and large granules (630-850 µm), respectively. The compression behavior of granules was characterized by the CBCS descriptors, and were compared with that of ungranulated powders. The relative change of tabletability (CoTr) index was used to establish the tabletability change classification system (TCCS), and all materials were classified into three types, i.e. loss of tabletability (LoT, Type I), unchanged tabletability (Type II) and increase of tabletability (Type III). Results showed that approximately 65% of materials presented LoT, and as the granules size increased, 84% of the materials exhibited LoT. A risk decision tree was innovatively proposed by joint application of the CBCS tabletability categories and the TCCS tabletability change types. It was found that the LoT posed little risk to the tensile strength of the final tablet, when Category 1 or 2A materials, or Category 2B materials with Type II or Type III change of tabletability were used. Formulation risk happened to Category 2C or 3 materials, or Category 2B materials with Type I change of tabletability, particularly when high proportions of these materials were involved in tablet formulation. In addition, the risk assessment results were verified in the material property design space developed from a latent variable model in prediction of tablet tensile strength. Overall, results suggested that a combinational use of CBCS and TCCS could aid the decision making in selecting materials for tablet formulation design via RCDG.

Intensified conditioning regimen with fludarabine combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in children with high-risk acute leukemia.

OBJECTIVE: Post-transplantation cyclophosphamide (PTCy) can reduce the incidence of graft versus host disease (GVHD) and this intervention is often applied on adults with hematologic malignancy. However, the high relapse rate hinders the development of the intervention and data of PTCy used on children with hematologic malignancy remains limited. In order to overcome issue of high relapse rate in PTCy treatment, we used fludarabine (Flu), enhanced dose of cytarabine (Ara-C, 9 g/m2), busulfan (Bu), Cy, anti-thymocyte globulin (ATG) combined with PTCy for an intensified conditioning regimen. METHODS: A total of 22 children with acute leukemia received intensified PTCy conditioning regimen (PTCy intensified group). We matched with 18 children who received modified Bu-Cy and ATG conditioning regimen in the same period (ATG group). RESULTS: The two-year cumulative incidences of grade II-IV acute GVHD was significantly lower in PTCy intensified group (13.6 ± 7.7% vs 38.9 ± 11.5%, P = 0.048). Two-year GVHD-free relapse free survival (GRFS) in PTCy seems to be better among the increment group despite not being significant (63.3 ± 10.3% vs 35.4 ± 11.9%, P = 0.092). The positive rate of minimal residual disease after transplantation was significantly lower than that before transplantation (20.0% vs 2.5%, P = 0.029). CONCLUSION: In conclusion, ATG and PTCy combined with Flu-based increased intensity conditioning regimen is effective for acute leukemia in children. It could reduce GVHD rate significantly and potentially improve GRFS.

[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(â ): classification of processing routes].

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Colorimetric and antioxidant films based on biodegradable polymers and black nightshade (Solanum nigrum L.) extract for visually monitoring Cyclina sinensis freshness.

In this study, colorimetric and antioxidant films were developed by using cassava starch (CS), κ-carrageenan (KC) and black nightshade fruit anthocyanins (BNA), and their physical and functional properties were investigated. We found BNA presented significant color changes in different pH solutions. And incorporation of BNA significantly increased the tensile strength, water vapor permeability, UV-vis light barrier property, pH-sensitivity and antioxidant activity of CS-KC film. Results of structural characterization indicated that H-bonds were formed between CS, KC and BNA in films and the film compactness was significantly improved by BNA incorporation. Results of the rheological property assay showed the films had high apparent viscosity with an obvious shear-thinning behavior. When applied to monitoring the quality change of Cyclina sinensis, CS-KC-BNA films exhibited significant color changes with the degradation process of C. sinensis qualities. Our results suggested CS-KC-BNA films could be utilized in smart packaging in food industry.

Learning Multi-Agent Cooperation via Considering Actions of Teammates.

Recently value-based centralized training with decentralized execution (CTDE) multi-agent reinforcement learning (MARL) methods have achieved excellent performance in cooperative tasks. However, the most representative method among these methods, Q-network MIXing (QMIX), restricts the joint action Q values to be a monotonic mixing of each agent's utilities. Furthermore, current methods cannot generalize to unseen environments or different agent configurations, which is known as ad hoc team play situation. In this work, we propose a novel Q values decomposition that considers both the return of an agent acting on its own and cooperating with other observable agents to address the nonmonotonic problem. Based on the decomposition, we propose a greedy action searching method that can improve exploration and is not affected by changes in observable agents or changes in the order of agents' actions. In this way, our method can adapt to ad hoc team play situation. Furthermore, we utilize an auxiliary loss related to environmental cognition consistency and a modified prioritized experience replay (PER) buffer to assist training. Our extensive experimental results show that our method achieves significant performance improvements in both challenging monotonic and nonmonotonic domains, and can handle the ad hoc team play situation perfectly.