[Correlation between weight variability and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus].

Objective: To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study. The clinical data of 2 180 T2DM patients without DKD who underwent case management at Lee's United Clinic in Taiwan, China from 2002 to 2018 were retrospectively analyzed, including 1 103 females and 1 077 males, with an average age of (64.8±12.4) years. Regular follow-up was conducted for patients for at least 2 years, and their metabolic indexes were monitored annually. BMI variability independent of the mean (BMI-VIM), average yearly mean square successive difference (BMI-ASV), coefficient of variation (BMI-CV) and standard deviation (BMI-SD) were calculated,based on the body mass index (BMI) recorded annually by the patients. Patients were divided into four groups (Q1-Q4) based on the quartiles of the four weight variability indexes. DKD group and non-DKN group(NDKD group) were defined based on the occurrence of DKD at the end of the follow-up. Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD. Subgroup analysis was performed by categorizing patients into non-obesity (BMI<28 kg/m2) and obesity groups (BMI≥28 kg/m2) to investigate the impact of the four weight variability indicators on the risk of DKD. Results: After a follow-up of (4.55±2.13) years, 904 patients developed DKD. Compared with the NDKD group, patients in the DKD group had a higher proportion of females, older age, longer duration of diabetes, more insulin users, higher waist-to-hip ratio, higher levels of BMI-VIM, BMI-ASV, BMI-CV, BMI-SD, systolic blood pressure, diastolic blood pressure, and urine albumin-creatinine ratio, a lower proportion of hypoglycemic drugs, estimated glomerular filtration rate, and high-density lipoprotein cholesterol level, with statistically significant differences between the two groups(all P<0.05). Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD, BMI-CV, BMI-VIM, and BMI-ASV after correcting a series of influencing factors. In the BMI-VIM subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.4% [HR=1.224 (95%CI:1.008-1.487), P=0.041]. In the BMI-ASV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 51.1% [HR=1.511 (95%CI:1.240-1.841), P<0.01]. In the BMI-CV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.006-1.485), P=0.044]. In the BMI-SD subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.002-1.490), P=0.048]. Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.551 (95%CI:1.228-1.958), P<0.001];when the obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.703 (95%CI:1.168-2.485), P=0.006]. Conclusion: Increases in BMI-VIM, BMI-ASV, BMI-CV, and BMI-SD are associated with an increased risk of DKD in T2DM patients.

Magnetic properties and critical behaviors of the nodal-line semimetal candidate ErIn3.

The AuCu3-type intermetallic compoundsReIn3(Re= a rare earth ion) with type-IV magnetic space groups are predicted to show topologically nontrivial electronic states. Here, we grow ErIn3single crystals, and study their magnetic properties and critical behaviors by means of the magnetic susceptibility, and magnetization isotherm measurements. Combining a detailed analysis of the magnetic susceptibility and isothermal magnetization, we find that this compound harbors a complicated magnetic phase diagram, and its magnetic moment arrangement appears not to simply follow the fashion as observed in the isostructural counterpart GdIn3(it adopts a conventional type-Cmagnetic structure that belongs to type-IV magnetic space groups). A careful study of the magnetic properties around the antiferromagnetic (AFM)-paramagnetic transition yields the critical exponentsß= 0.309 (0.297),γ= 1.117 (1.038), andδ= 4.617 (4.454), indicating that the tricritical mean field model or the three-dimensional Ising model works for ErIn3's magnetic behaviors and the presence of a long-range AFM interaction therein. Besides, the exchange interaction distanceJ(r) ∼r-4.665as well confirms a long-range magnetic coupling in ErIn3. Our results offer the clues that the magnetic structure varies from one member ofReIn3family to another, and to confirm their electronic features in the AFM phases further experimental and theoretical studies are still desired.

[Clinical evaluation of ventricular septal defect occlusion device for the treatment of postoperative bronchopleural fistula].

Bronchopleural fistula is an abnormal sinus tract that forms between the bronchus and the thoracic cavity. It is most commonly caused by thoracic surgery. Patients often have severe pulmonary and thoracic infections, which seriously affect the quality of life and survival rate. Most of these patients do not have a second operation chance, so the bronchopleural fistula becomes a thorny problem in the clinical practice. The clinical data of 9 patients with postoperative bronchopleural fistula admitted to Anhui Provincial Chest Hospital were reviewed and analyzed. We analyzed and summarized the clinical experience of successful occlusion with a ventricular septal defect(VSD) device, which provided a potentially effective treatment for postoperative bronchopleural fistula.

Anisotropic magnetoresistance and electronic features of the candidate topological compound praseodymium monobismuthide.

PrBi, a sister member of the rare-earth monopnictide family, is an excellent candidate for studying extreme magnetoresistance and nontrivial topological electronic states. In this study, we perform angular magnetoresistance measurements as well as bulk and surface band structure calculations on this compound. PrBi's magnetoresistance is revealed to be significantly angle-dependent and shows a fourfold symmetry as always observed in the nonmagnetic isostructural counterparts, including LaSb, LaBi, and LuBi. Its angular magnetoresistance can be reproduced well using the semiclassical two-band model. The deduced parameters suggest that PrBi hosts an elongated electron pocket with a mobility anisotropy of ∼3.13 and is slightly uncompensated in its carrier concentration. Our bulk and surface band structure calculations confirm the anisotropic electronic features. Moreover, we reveal that a nodal-line-shaped surface state appears at the X̄ point, and is associated with the quadratic dispersion along the -X̄ direction, and the linear type-I Dirac dispersion along the X̄-M̄ direction. Owing to the type-I Dirac dispersion feature, PrBi could serve as a promising material platform for studying many unexpected physical properties, such as the highly anisotropic transport and valley polarization of electrons.

[Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment].

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data.

OBJECTIVES: To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans. DESIGN: Test-negative case-control study of SARS-CoV-2 mRNA vaccine effectiveness. SETTING: Veterans Health Administration (VHA) medical centers. PARTICIPANTS: Veterans 19 years and older who had at least one COVID-19/Flu like symptoms and received a SARS-CoV-2 PCR or antigen test at VHA medical centers between July 25 to September 30, 2021. INTERVENTION: mRNA vaccination. MEASUREMENTS: New SARS-CoV-2 infection. Vaccine effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls, where cases were patients who had a COVID-19 test and tested positive for SARS-CoV-2, and controls were those who tested negative. Frailty was measured using the VA frailty index, categorized as robust (0-<0.1), pre-frail (≥0.1-<0.21) and frail (≥0.21). RESULTS: A total of 58,604 patients (age:58.9±17.0, median:61, IQR:45-72; 87.5%men; 68.1%white; 1.3%African American, 8.3%Hispanic) were included in the study. Of these, 27,733 (47.3%) were robust, 16,276 (27.8%) were prefrail, and 14,595 (24.9%) were frail. mRNA vaccine effectiveness against the Delta variant symptomatic infection was lower in patients with frailty, 62.8 %(95%CI:59.8-65.7), versus prefrail 73.9%(95%CI:72.0-75.7), and robust, 77.0 %(95%CI:75.7-78.3). CONCLUSIONS: This test-negative case control study showed that mRNA vaccine effectiveness against infection declined in veterans with frailty. Frailty status is a factor to consider when designing, developing, and evaluating COVID-19 vaccines.

Advancing NMR-based metabolomics using complete reduction to amplitude frequency table: Cultivar differentiation of black ripe table olives as a case study.

In NMR-based untargeted analysis, Fourier transformation is applied to the time-domain data to extract observables such as frequency and intensity. Despite its wide application, this approach has several limitations that can prevent NMR from reaching its highest potential. Here, we utilized Bayesian analysis through CRAFT as an alternative method, using California-style table olives as a model system. Our hypothesis was that the time-domain analysis through CRAFT will be as successful as the traditional approach. The results showed that CRAFT generated efficient unsupervised and supervised models in a robust, and rapid/automated manner. The duration of CRAFT analysis can be further reduced by using the first 14 k complex data points of the initial part of the FID, without affecting the performance of the untargeted analysis. For unsupervised analysis, CRAFT was generally more efficient, while for supervised analysis both approaches were effective. CRAFT can be also used for identifying marker compounds driving classifications.

[The value of MR diffusion tensor imaging in assessing white matter changes in short-term methamphetamine withdrawal].

Objective: To explore the value of MRI diffusion tensor imaging (DTI) in the white matter changes of short-term methamphetamine (MA) abstinence. Methods: The data of DTI, demographics features, general information of addiction and impulsivity scale eleven (BIS-11) of 55 short-term MA addicts who were from Changsha, Zhuzhou and Yueyang compulsory detoxification centers in Hunan province, including 40 males and 15 females, aged 14-45 (37.24±7.31) years old, and 52 healthy controls, including 40 males and 12 females aged 18-59 (40.3±9.1) years were collected prospectively from August 2017 to December 2018. The differences of DTI indicators between the two groups were compared by tract-based spatial statistics (TBSS), and then the correlation between the different indicators and the age of first MA use, time of MA use, daily dose used, BIS-11 score were performed. Results: There were significant differences in BIS total score(P<0.001), BIS motivational impulsivity(P<0.001) and BIS attentional impulsivity(P=0.003) between MA group and healthy control group in short-term withdrawal. And compared with the healthy control group, the fractional anisotropy (FA) (0.58±0.02 vs 0.56±0.02,0.77±0.02 vs 0.75±0.04,0.79±0.04 vs 0.76±0.06; all P<0.05), axial diffusivity (AD) (0.57±0.01 vs 0.56±0.02,P=0.001) and mean diffusivity (MD) (0.66±0.02 vs 0.65±0.02,0.52±0.07 vs 0.51±0.06; both P<0.05)values in the MA group were all increased (P<0.05), but there was no significant difference in the radial diffusivity (RD) value (P>0.05). The white matter areas with increased FA value were located in the knee and body of corpus callosum, bilateral anterior corona radiata and left superior corona radiata; the areas with increased AD value were located in the knee, body and pressure of corpus callosum, bilateral anterior limb of internal capsule, posterior limb of internal capsule, anterior, superior and posterior corona radiata, external capsule and superior longitudinal fasciculus; and the areas with increased MD value were mainly located in the right superior longitudinal fasciculus, anterior and posterior limb of internal capsule. The corpus callosum, where there was a difference in FA between the two groups, was positively correlated with the daily dose of MA (r=0.301, P=0.026). Conclusion: MA addicted individuals with short-term withdrawal have white matter edema and damage, and the degree of corpus callosum damage is positively correlated with the daily dose of MA,which is helpful to understand the pathophysiological process of white matter damage in the nervous system and the potential mechanism of neuropsychiatric symptoms in short-term withdrawal MA addicted individuals.

[Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation].

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

[Scanning electron microscopic observation of the external morphology of Dermatophagoides farinae at different developmental stages].

OBJECTIVE: To investigate the morphological characteristics of Dermatophagoides farinae at different developmental stages. METHODS: The cultured D. farinae was isolated, and the external morphological features of mites at various developmental stages were observed using scanning electron microscopy (SEM), including egg, larva, nymph and adult stages. RESULTS: The D. farinae egg appeared a long oval shape, and the larval mites had three pairs of legs. The nymph had four pairs of legs and underdeveloped genital pores containing genital setae and anal setae, and adult mites appeared long and oval in shape, with decorative patterns on epidermis, and had four pairs of legs. In male adult mites, remarkable thickening of the leg I and thicker and longer leg III than the leg IV were seen, and ventral genital regions were found between the basal segments of legs III and IV; the anus was surrounded by a circular peri-anal ring, with a pair of anal suckers and anal setae within the ring. In the female adult mites, slender legs III and IV with an equal length were seen, and a "λ-shape" genital hole was observed on the ventral surface, with a crescent-like genital plate in the anterior part, and the anus appeared a longitudinal slit. CONCLUSIONS: An SEM observation of the external morphology of D. farinae provides understandings of the morphological characteristics of D. farinae, which is of great significance for the classification and identification.

[The value of CXorf67 and H3K27me3 for diagnosing germ cell tumors in central nervous system].

Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r2=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.

Emerging Issues Questioning the Current Treatment Strategies for Lumbar Disc Herniation.

Lumbar disc herniation is among the common phenotypes of degenerative lumbar spine diseases, significantly affecting patients' quality of life. The practice pattern is diverse. Choosing conservative measures or surgical treatments is still controversial in some areas. For those who have failed conservative treatment, surgery with or without instrumentation is recommended, causing significant expenditures and frustrating complications, that should not be ignored. In the article, we performed a literature review and summarized the evidence by subheadings to unravel the cons of surgical intervention for lumbar disc herniation. There are tetrad critical issues about surgical treatment of lumbar disc herniation, i.e., favorable natural history, insufficient evidence in a recommendation of fusion surgery for patients, metallosis, and implant removal. Firstly, accumulating evidence reveals immune privilege and auto-immunity hallmarks of human lumbar discs within the closed niche. Progenitor cells within human discs further expand the capacity with the endogenous repair. Clinical watchful follow-up studies with repeated diagnostic imaging reveal spontaneous resolution for lumbar disc herniation, even calcified tissues. Secondly, emerging evidence indicates long-term complications of lumbar fusion, such as adjacent segment disease, pseudarthrosis, implant failure, and sagittal spinal imbalance, which get increasing attention. Thirdly, systemic and local reactions (metallosis) for metal instrumentation have been noted with long-term health concerns and toxicity. Fourthly, the indications and timing for spinal implant removal have not reached a consensus. Other challenging issues include postoperative lumbar stiffness. The review provided evidence from a negative perspective for surgeons and patients who attempt to choose surgical treatment. Collectively, the emerging underlying evidence questions the benefits of traditional surgery for patients with lumbar disc herniation. Therefore, the long-term effects of surgery should be closely observed. Surgical decisions should be made prudently for each patient.

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience].

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Mucoadhesive Nucleoside-Based Hydrogel Delays Oral Leukoplakia Canceration.

Some oral squamous cell carcinomas (OSCCs) originate from preexisting oral potentially malignant disorders (OPMDs). Oral leukoplakia (OLK) is the most common and typical OPMD in the clinic, so treatment for it is essential to reduce OSCC incidence. Local chemotherapy is an option other than surgery considering the superficial site of OLK. However, there are no standardized drugs applied to OLK, and traditionally used chemotherapeutic drugs revealed limited efficacy for lack of adhesion. Hence, there is a growing demand to prepare new agents that combine mucoadhesion with an anti-OLK effect. Here, an isoguanosine-tannic acid (isoG-TA) supramolecular hydrogel via dynamic borate esters was successfully fabricated based on isoG and TA. Previously reported guanosine-TA (G-TA) hydrogel was also explored for an anti-OLK effect. Both gels not only exhibited ideal adhesive properties but also integrated anti-OLK activities in one system. In vitro cell viability indicated that isoG and TA inhibited the proliferation of dysplastic oral keratinocytes (DOKs). The in vivo OLK model evidence revealed that both gels showed potential to prevent OLK canceration. In addition, the probable anti-DOK mechanisms of isoG and TA were investigated. The results indicated that isoG could bind to adenosine kinase (ADK) and then affected the mammalian target of rapamycin (mTOR) pathway to inhibit DOK proliferation. TA could significantly and continuously reduce reactive oxygen species (ROS) in DOKs through its antioxidant effect. ROS plays an important role in the progression of cell cycle. We proved that the low level of ROS may inhibit DOK proliferation by inducing G0/G1 arrest in the cell cycle. Altogether, this study innovatively fabricated an isoG-TA hydrogel with ideal adhesion, and both isoG and TA showed in vitro inhibition of DOKs. Moreover, both isoG-TA and G-TA hydrogels possessed potential in delaying the malignant transformation of OLK, and the G-TA hydrogel showed a better statistical effect, providing an effective strategy for controlling OLK.