Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective:To investigate the effect of Fu-Fang-Yu-Jie(FFYJ)granules on LPS-induced inflammation model in bone marrow-derived macrophages(BMDM)and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammatory signaling pathway in macrophages.Methods:Primary cells were extracted and isolated from the leg bone mar-row of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF.Groups included control group(Control),model group(LPS+ATP),FFYJ low dose group(FFYJ 50 μg/ml),FFYJ medium dose group(FFYJ 100 μg/ml),FFYJ high dose group(FFYJ 200 μg/ml)and positive drug dexamethasone group(DEX).BMDM in FFYJ treatment group and posi-tive drug group were pretreated for 1 hour before modeling.Lactate dehydrogenase(LDH)release assay was used to detect the level of LDH in the supernatant of each group of cells;ELISA was used to detect the level of inflammatory factors TNF-α,IL-6 and IL-1β in the supernatant of each group of cells;qRT-PCR was used to detect the levels of TNF-α,IL-6 and IL-1β in each group of cells;protein levels of NF-κB,p-NF-κB,NLRP3,Caspase-1 p45,Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot;inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining.Results:Compared with control group,the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of the model group were signifi-cantly higher(P<0.000 1);the mRNA levels of TNF-α,IL-6 and IL-1β in the model group were significantly higher(P<0.000 1);the protein levels of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N were significantly higher(P<0.05);and the number of PI-posi-tive cells was significantly higher(P<0.05).Compared with the model group,FFYJ and DEX significantly reduced the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of BMDMs(P<0.05);down-regulated the mRNA levels of TNF-α,IL-6 and IL-1β in the cells(P<0.05);and inhibited the expressions of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N protein expressions(P<0.05);and significantly reduced the number of PI-positive cells(P<0.05).Conclusion:FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages.

Objective:To analyze and summarize the clinical characteristics of mpox patients, thereby to rise clinicians′ awareness of severe mpox and provide a foundation for clinical diagnosis and treatment.Methods:The clinical data were retrospectively analyzed in 41 mpox patients treated at the Beijing You′an Hospital, Capital Medical University, from June to November 2023. Patients were categorized into mild and severe cases based on clinical manifestations, and laboratory results of the two groups were compared. Statistical analysis was performed using the Mann-Whitney U test. Results:The clinical manifestations of 41 mpox patients mainly included fever, rash and lymphadenopathy. Five patients with severe mpox might develop serious complications, including bacterial pneumonia, type Ⅰ respiratory failure, fungal infections, penile or perianal dry gangrene, penile soft tissue edema, intestinal obstruction, septic shock, perianal abscess, and necrotizing fasciitis. Patients with severe mpox had significantly higher white blood cell count (WBC), neutrophil count and C-reactive protein (CRP) level compare to those with mild cases (14.60(9.92, 24.08)×10 9/L vs 6.41(5.64, 8.37)×10 9/L, 12.43(7.02, 21.15)×10 9/L vs 3.35(2.46, 5.03)×10 9/L, 108.20(56.20, 124.10) mg/L vs 16.6(6.25, 49.98) mg/L), while the albumin level and CD4 + T lymphocyte count in the severe group were significantly lower compared to the mild cases (31.80(22.90, 35.15) g/L vs 44.70(42.90, 47.40) g/L, 24.00(12.00, 81.50)/μL vs 606.00(414.50, 767.50)/μL)). All these differences were statistically significant ( U=2.81, 3.02, 2.98, 3.56 and 3.26, respectively, all P<0.01). Conclusions:In clinical practice, clinicians should be vigilant for the possibility of severe mpox if patients exhibit a significant increase of WBC and CRP, a significant decrease in CD4 + T lymphocyte count, or if they develop severe complications.

Objective To investigate the differences in efficacy and safety in the treatment of patients with cerebral palsy at different grades of the Gross Motor Function Classification System (GMFCS) by selective posterior rhizotomy (SPR). Methods Relevant literatures on SPR treatment for cerebral palsy were retrieved from Pubmed, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database. Clinical trials on SPR treatment for cerebral palsy were included for Meta-analysis. At least two researchers independently screened the literatures, extracted data, and assessed the quality of the literatures. Data analysis was performed by Review Manager 5.4 software. Results A total of 2, 726 literatures were retrieved, and 8 literatures were finally included after screening. The results of the Meta-analysis showed that the gross motor function and self-care ability of patients with cerebral palsy at all GMFCS grades improved significantly after surgery, and muscle tone decreased significantly after surgery (P < 0.05). In comparison of the improvement in gross motor function before and after SPR, patients with grades Ⅱ and Ⅲ of GMFCS benefited the most, followed by those with grade Ⅰ, and those with grades Ⅳ and V benefited less. In terms of improving self-care ability, patients with grade Ⅰ benefited the most, followed by those with grade Ⅲ, and those with grades Ⅱ and IV benefited less. No significant adverse reactions were reported in previous literatures. Conclusion SPR is a relatively safe and effective treatment option for patients with cerebral palsy. Patients at grades Ⅱ and Ⅲ of GMFCS benefit the most from SPR, and patients at grades Ⅳ and V with poor preoperative physical status can also benefit from SPR.

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].

Objective:To investigate the correlation of serum testosterone level with severity and characteristics of coronary plaque, stent implantation rate and major cardiovascular adverse events(MACE)in elderly male patients with coronary heart disease(CHD).Methods:In this retrospective study, a total of 63 elderly male patients of the Third People's Hospital of Hangzhou with coronary angiography(CAG)-confirmed CHD and to undergo percutaneous coronary intervention(PCI)were selected.According to serum testosterone level, they were divided into the low testosterone(low T)group and the normal testosterone(normal T)group.Optical coherence tomography(OCT)was performed in both groups to define the characteristics of coronary artery lesions and guide stent implantation.The correlation of serum testosterone level with blood lipids, glycated hemoglobin(HbA1c), degree of coronary artery lesions, plaque characteristics, stent implantation and MACE in two groups were analyzed.The in-stent restenosis rate after stent implantation and the variation of minimum lumen diameter of stent were determined during 12 months follow up in both groups.Results:Total cholesterol(TC), low-density lipoprotein(LDL-C)and HbA1c were higher in the low T group than in the normal T group( t=7.808、-5.871、6.611, all P<0.05). When taking testosterone as the independent variable, and TC, triglycerides(TG), LDL-C, high density lipoprotein cholesterol(HDL-C)and HbA1c as the dependent variables, linear regression analysis showed that TC, LDL-C and HbA1c were negatively correlated with testosterone level( β=-0.733, -0.716, -0.581, P<0.05). More than 2 vascular lesions were more common in low testosterone group versus the control group( χ2=8.66, P<0.05). Mixed plaques, lipid plaques, and calcified plaques were more commonly found in low testosterone group versus the control group( χ2=7.87, P<0.05). Unstable plaques were more common in the low T group( χ2=6.14, P<0.05). The low T group vs the normal T group, coronary stent implantation rate were 93.3%(28/30 cases) vs.66.7%(22/33 cases), the difference was statistically significant( χ2=6.82, P<0.05). When testosterone, TC, TG, LDL-C, HDL-C, HbA1c were taken as the independent variables, and the stent implantation rate was the dependent variable, logistic regression analysis results showed that only testosterone, TC and HbA1c were independently correlated with stent implantation rate( OR=0.971、425.523、0.004, P<0.05). There was no statistically significant difference in minimum stent lumen diameters between the two groups under OCT-guided coronary stent implantation( t=-1.064, P>0.05). During 12 months follow up, the MACE0 incidence was 26.7%(8/30 cases, in low T group)than 6.1%(2/33 cases, in normal T group), with statistically significant difference( χ2=5.00, P<0.05). When taking testosterone, TC, TG, LDL-C, HDL-C and HbA1c as the independent variables, and MACE as the dependent variable, logistic regression analysis results showed that only testosterone and LDL-C were independently correlated with MACE( OR=0.968, 0.008, P<0.05). Conclusions:Serum testosterone level is negatively correlated with TC, LDL-C and HbA1c, and may be correlated with the degree of coronary artery lesions, plaque properties, MACE and stent implantation rate of CHD patients.Serum testosterone can be used to evaluate the characteristics and conditions of CHD, and help to predict the prognosis of CHD.The OCT is a good guide tool for coronary stent implantation.

Chronic heart failure(CHF) is the end stage of various cardiovascular diseases and is one of the common diseases among the elderly in China. Sarcopenia is a geriatric syndrome characterized by the age-related loss of skeletal muscle quantity and/or mass and the decline in muscle strength and/or physical performance. There is a common pathophysiological mechanism of CHF and sarcopenia, and they interact with each other and influence each other′s prognosis. There are few confirmed effective treatments for sarcopenia, and even fewer measures that can help slow the progression of both syndromes. However, on the basis of heart failure treatment hormone therapy, exercise training and nutritional support may slow the progression of sacopenia. This article reviews the recent advances in the relationship between elderly CHF patients with sarcopenia and related treatment.

Livestock husbandry is vital to economy of the Tarim Basin, Xinjiang Autonomous Region, China. However, there have been few surveys of the distribution of ixodid ticks (Acari: Ixodidae) and tick-borne pathogens affecting domestic animals at these locations. In this study, 3,916 adult ixodid ticks infesting domestic animals were collected from 23 sampling sites during 2012-2016. Ticks were identified to species based on morphology, and the identification was confirmed based on mitochondrial 16S and 12S rRNA sequences. Ten tick species belonging to 4 genera were identified, including Rhipicephalus turanicus, Hyalomma anatolicum, Rh. bursa, H. asiaticum asiaticum, and Rh. sanguineus. DNA sequences of Rickettsia spp. (spotted fever group) and Anaplasma spp. were detected in these ticks. Phylogenetic analyses revealed possible existence of undescribed Babesia spp. and Borrelia spp. This study illustrates potential threat to domestic animals and humans from tick-borne pathogens.