OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

Objective West Nile virus(WNV)is one of the most common mosquito-borne zoonotic viruses worldwide,with unique transmission dynamics and varied hosts.Lots of ecological and host factors have been reported to influence the host adaptation and transmission of WNVs,however,general genomic features of WNVs are less focused,except for some exact host-specific genotypes at molecular level.Artificial intelligence that analyzes genome composition characteristics currently shows significant advantages in identifying and predicting viral host adaptability.This research aimed to establish a convolutional neural network(CNN)model to predict the host adaptability of WNVs based on general genomic features.Methods Presently available WNV gene sequences were embedded for their genomic features with an embedding approach of dinucleotide composition representation(DCR).And DCR-based distribution difference of WNV samples among various hosts was performed with unsupervised learning methods.Then a classification model was built with a convolutional neural network(CNN)framework based on genomic DCR to evaluate the adaptation of the WNVs from birds,mammals and mosquitos.Additionally,host-specific amino acids in WNV proteins were inferred via Bayes method.Results DCR features could effectively distinguish host-specific WNVs.The trained CNN model predicted accurately mammalian susceptible WNVs from avian susceptible WNVs,however,much less accurately for mosquito/mammalian WNVs.Such predicted host adaptation was interpreted as host specified significance of biased amino acid distribution on the bayes-inferred sites in WNV proteins,implying a possible high significance of these sites for WNV adaptive phenotypes.Conclusions Genomic compositional features of WNVs are host-specific,and such genomic bias facilitates predicting the adaptation of WNVs to avian or mammalian hosts via deep learning methods.DCR-based decomposition is helpful to recognize the high risk of infecting mammals of WNVs.The present study provides a general knowledge of genomic features contributing to host adaptation to WNVs.

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Objective:To confirm the potential etiological factors of congenital aortic stenosis(AS)by genetic analysis on prenatal diagnostic results of the fetus with AS.Methods:Amniocentesis for chromosomal G-band karyotyping combinated with single nucleotide polymorphism array(SNP-array)analysis was conducted on the amniotic fluid collected from a 25-week pregnant woman diagnosed as"fetus AS";chromosome karyotyping was also performed on the peripheral blood of the fetal parents.Results:The fetal karyotype analysis showed a chimeric Y-chromosome isobaric double-adherent granules.The SNP-array analysis results revealed a 11.2 Mb duplication in the Yp11.31q11.21 region and a 14.8 Mb deletion in the Yq11.21q11.23 region.Both the parents presented a normal karyotype,suggesting it was a newfound mutation.After extensive genetic counseling,the pregnant woman and her family chose to terminate the pregnancy locally.Conclusion:The chromosomal karyotype of the chimeric Y-chromosome isobaric double-adherent granules may be a contributing factor to the AS phenotype in the male fetus.The combined use of chromosomal karyotyping and SNP-array analysis on the amniotic cells is instrumental in the early diagnosis of the disease.

Objective:To compare the short-term outcomes of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants supplementarily fed with fortified donor human milk (DHM) or preterm formula (PF) when the mother's own milk (MOM) is insufficient.Methods:This retrospective cohort study included 91 VLBW or ELBW preterm infants with birth weight<1 500 g who were hospitalized in Peking Union Medical College Hospital from October 1, 2017, to September 30, 2020. Based on the supplemental feeding method when MOM was insufficient, these infants were divided into the DHM group ( n=51) and PF group ( n=40). Mann-Whitney U, t-test, Chi-square test, or Fisher's exact test were used to compare the short-term clinical outcomes during hospitalization between the two groups. Results:(1) There were no statistically significant differences between the 91 preterm infants in the DHM group and PF group in their gestational age, birth weight, sex ratio, birth mode, mothers' age at delivery, or the proportion of infants of small gestational age (all P>0.05). (2) The feeding volume in the DHM group was significantly greater than that in the PF group on the 14th day after birth [(108.2±53.1) vs. (81.0±47.8) ml/(kg·d), t=0.78, P=0.020]. Moreover, the time to achieve the feeding amounts up to 120 ml/(kg·d) and 150 ml/(kg·d) for infants in the DHM group were significantly shorter than those in the PF group [(17.5±10.2) vs. (30.0±12.0) d, t=4.38; (22.1±13.3) vs. (32.3±11.9) d, t=0.02; both P<0.05]; (3) Lower proportion of peripherally inserted central catheter (PICC) [58.8% (30/51) vs. 100% (40/40), χ 2=21.88, P<0.001] and shorter PICC duration were observed in the DHM group [10.0 (0.0-19.0) vs. 29.0 (17.0-40.5) d, Z=5.56, P<0.001] compared to the PF group. The times of red blood cell transfusions and the incidence of late sepsis in the DHM group were less than those in the PF group [0.0 (0.0-2.0) vs. 2.0 (1.0-3.0) times, Z=4.44, P<0.001; 23.5% (12/51) vs. 50.0% (20/40), χ 2=6.39, P=0.011]. There were no statistically significant differences observed in the incidence of bronchopulmonary dysplasia, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the length of hospitalization (all P>0.05). Conclusion:When MOM is insufficient, supplementing VLBW and ELBW infants with fortified donor human milk can shorten the time to achieve enteral nutrition and reduce the use rate and time of PICC, the incidence of late-onset sepsis, and the times of red blood cell transfusion.

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Objective:To analyze the epidemiological characteristics and pathogen spectrum of influenza outbreaks in Shaanxi Province from 2014 to 2023 and provide basis reference for strengthening regional influenza prevention and control.Methods:The data were collected from the Public Health Emergency Management Information System of the China Disease Prevention and Control Information System and the China Influenza Surveillance Information System. On-site epidemiological investigation information and etiological test results of influenza network laboratories reported in Shaanxi Province during 2014-2023 were collected, and descriptive analysis was conducted on the time, region, and location distribution of influenza outbreaks. SPSS 25.0 software was used for statistical analysis.Results:A total of 386 influenza outbreaks were reported in Shaanxi from 2014 to 2023, with a total attack rate of 1.81% (14 880/821 001). The epidemic peaks mainly occurred in winter and spring (November to March of the following year), and there was an alternating pattern of epidemic peaks in different years (the early peak was in December, and the late peak was in March of the following year). The epidemic areas were mainly concentrated in the Qinba Mountains of southern Shaanxi (209, 54.15%) and Guanzhong Plain (173, 44.82%). The epidemic places were mainly distributed in primary schools (239, 61.92%), and the differences of epidemic areas and places were statistically significant (all P<0.001). Influenza A(H3N2) viruses were the predominant pathogen in the outbreak (849, 57.76%), and influenza A(H3N2), B (Victoria) lineage and A(H1N1)pdm09 virus alternately dominated the epidemic peak in different years. Conclusions:The peak of influenza outbreaks in Shaanxi Province was winter and spring during 2014-2023. Primary schools in the Qinba Mountains of southern Shaanxi and Guanzhong Plain should be targeted for prevention and control. In the prevention and control programs, close attention should be paid to the changing trend of dominant strains. Effective intervention measures should be targeted to the high-incidence areas and seasons.

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.