Artificial intelligence (AI) researchers and cheminformatics specialists strive to identify effective drug precursors while optimizing costs and accelerating development processes. Digital molecular representation plays a crucial role in achieving this objective by making molecules machine-readable, thereby enhancing the accuracy of molecular prediction tasks and facilitating evidence-based decision making. This study presents a comprehensive review of small molecular representations and AI-driven drug discovery downstream tasks utilizing these representations. The research methodology begins with the compilation of small molecule databases, followed by an analysis of fundamental molecular representations and the models that learn these representations from initial forms, capturing patterns and salient features across extensive chemical spaces. The study then examines various drug discovery downstream tasks, including drug-target interaction (DTI) prediction, drug-target affinity (DTA) prediction, drug property (DP) prediction, and drug generation, all based on learned representations. The analysis concludes by highlighting challenges and opportunities associated with machine learning (ML) methods for molecular representation and improving downstream task performance. Additionally, the representation of small molecules and AI-based downstream tasks demonstrates significant potential in identifying traditional Chinese medicine (TCM) medicinal substances and facilitating TCM target discovery.
Artificial Intelligence ; Drug Discovery/methods* ; Humans ; Machine Learning ; Medicine, Chinese Traditional ; Small Molecule Libraries/chemistry*

Objective To investigate the levels of γδ T cells and their subpopulations in bone marrow(BM)of patients with myelodysplastic syndrome(MDS),it aims to explore the immune deficiency status of BM microenvi-ronment in MDS patients.Methods BM samples were collected from MDS patients before and after treatment,as well as from normal donors.Multicolor flow cytometry was utilized to detect bone marrow γδ T cells and subpopulation levels.The changes of the T cell subsets after treatment were also analyzed.Results The levels of BM γδ T cells and follicular helper γδ T cells from MDS patients were significantly lower than those of normal donors(P<0.05).Among γδ T cells at different stages of differentiation,only the frequencies of na?ve γδ T cells from MDS patients decreased significantly(P = 0.037),and there was no significant difference observed about central memory,effector memory,and terminally differentiated γδ T cells in MDS patients compared to normal donors(P>0.05).Although there was a slight decrease in PD1+γδ T cells and an increase in TIM3+γδ T cells,these differences were not statistically significant(P>0.05).In patients who achieved a curative effect,the proportions of γδ T cells and naive γδ T cells increased significantly after treatment,and the effector memory γδ T cells decreased significantly after treatment(P<0.05).After treatment,85.71%(6/7)of MDS patients showed a decrease in γδ+TIM3+ T cell levels to varying degrees.Conclusions The levels of γδ T cells and their subpopulations in the BM microenvironment of patients with MDS exhibit varying degrees of abnormalities.However,in patients who receive effective treatment,these abnormal γδ T cells can recover.By detecting the levels of γδ T cells and subpopulations,we can gain insights into the immune deficiency status of MDS.This information might serve as an indicator to assess treatment efficacy and provide valuable insights for anti-tumor immunotherapy.

OBJECTIVE: To establish a rapid detection and genotyping method for SARS-CoV-2 Omicron BA.4/5 variants using CRISPPR-Cas12a gene editing technology. METHODS: We combined reverse transcription-polymerase chain reaction (RT-PCR) and CRISPR gene editing technology and designed a specific CRISPPR RNA (crRNA) with suboptimal protospacer adjacent motifs (PAM) for rapid detection and genotyping of SARS- CoV-2 Omicron BA.4/5 variants. The performance of this RT- PCR/ CRISPPR-Cas12a assay was evaluated using 43 clinical samples of patients infected by wild-type SARS-CoV-2 and the Alpha, Beta, Delta, Omicron BA. 1 and BA. 4/5 variants and 20 SARS- CoV- 2-negative clinical samples infected with 11 respiratory pathogens. With Sanger sequencing method as the gold standard, the specificity, sensitivity, concordance (Kappa) and area under the ROC curve (AUC) of RT-PCR/CRISPPR-Cas12a assay were calculated. RESULTS: This assay was capable of rapid and specific detection of SARS- CoV-2 Omicron BA.4/5 variant within 30 min with the lowest detection limit of 10 copies/μL, and no cross-reaction was observed in SARS-CoV-2-negative clinical samples infected with 11 common respiratory pathogens. The two Omicron BA.4/5 specific crRNAs (crRNA-1 and crRNA-2) allowed the assay to accurately distinguish Omicron BA.4/5 from BA.1 sublineage and other major SARS-CoV-2 variants of concern. For detection of SARS-CoV-2 Omicron BA.4/5 variants, the sensitivity of the established assay using crRNA-1 and crRNA-2 was 97.83% and 100% with specificity of 100% and AUC of 0.998 and 1.000, respectively, and their concordance rate with Sanger sequencing method was 92.83% and 96.41%, respectively. CONCLUSION By combining RT-PCR and CRISPPR-Cas12a gene editing technology, we successfully developed a new method for rapid detection and identification of SARS-CoV-2 Omicron BA.4/5 variants with a high sensitivity, specificity and reproducibility, which allows rapid detection and genotyping of SARS- CoV-2 variants and monitoring of the emerging variants and their dissemination.
Humans ; COVID-19 ; CRISPR-Cas Systems ; Genotype ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; SARS-CoV-2/genetics* ; RNA ; COVID-19 Testing

Hepatocellular carcinoma （HCC）， an insidious malignant tumor with high incidence and lethality， poses a major threat to physical and mental health of human beings. The pathological mechanism needs to be further studied. Surgery， radiotherapy， chemotherapy， and targeted drugs are effective but induce many adverse reactions. Traditional Chinese medicine （TCM） has unique advantages and abundant clinical experience in the treatment of HCC. There has been an explosion of research on the pathways， targets， and mechanism of TCM against HCC from the perspective of molecular biology. According to previous research， Chinese medicinals or compound Chinese medicine prescriptions， directly or indirectly prevent the occurrence and progression of HCC through multiple pathways and targets， which is closely related to the pathophysiological processes such as cell proliferation， metastasis， apoptosis， autophagy， inflammatory response， and immune response. This paper summarizes and analyzes research on the action pathways and mechanisms of Chinese medicine against HCC. Specifically， isoliquiritigenin， dendrobium candidum and Yexiazhu compound Ⅱ regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the growth， proliferation and metastasis of tumor cells. Toad venom and dioscorea zingiberensis induce and enhance HCC autophagy by modulating mammalian target of rapamycin （mTOR） signaling pathway. Myricetin， asparagus， and Biejiajian Wan regulate mitogen-activated protein kinase （MAPK） signaling pathway to promote HCC cell cycle arrest， inhibit angiogenesis， and induce apoptosis. Polygonum odoratum， tetragonum， and plantainoside modulate nuclear factor-kappa B （NF-κB） to inhibit inflammatory response and HCC metastasis and reduce drug resistance. Quercetin and erigeron breviscapus control the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway to suppress epithelial-mesenchymal transition （EMT） and remodel cytoskeleton. This paper is expected to lay a theoretical basis for the in-depth research on and clinical application of Chinese medicine in the treatment of HCC.

Objective: To monitor the WT1 mRNA level and its dynamic changes in patients with myelodysplastic syndromes (MDS) after hypomethylating agents (HMA) , as well as to assess the significance of WT1 mRNA levels and its dynamic changes in evaluating the efficacy of HMA and distinguishing the disease status of heterogeneous patients with stable disease (SD) . Methods: Bone marrow or peripheral blood samples of 56 patients with MDS who underwent hypomethylating agents (≥4 cycles) from November 2009 to March 2018 were tested by real-time quantitative polymerase chain reaction (PCR) to detect the expression of WT1 mRNA, and to observe the correlation between the dynamic changes of WT1 mRNA expression and clinical efficacy and prognosis of patients. Results: WT1 mRNA expression levels of MDS patients decreased significantly after 3 cycles of hypomethylating agent treatment. Besides, the WT1 mRNA expression levels of patients increased significantly after diseases progression. According to the dynamic changes of WT1 mRNA expression levels during SD, 45 cases could be further divided into increased group and non-increased group. In those SD patients with increased WT1 mRNA expression level, the ratio of suffering disease progression or transformation to AML was 95.65% (22/23) , whereas the ratio turned to be 9.09% (2/22) for the non-increased group (χ²=33.852, P<0.001) . Compared with those SD patients reporting no increase in WT1 mRNA expression level, the overall survival[17 (95%CI 11-23) months vs not reached, P<0.001] and progression-free survival [13 (95%CI 8-18) months vs not reached, P<0.001] of those SD patients reporting increase in WT1 mRNA expression level were significantly shorter. Conclusion WT1 mRNA expression level is a useful indicator to assess the efficacy of hypomethylating agents in MDS patients. Especially in patients with SD, detection of the changes in WT1 mRNA expression level is able to predict disease progression and help to make clinical decision.

Objective]In order to study the impact of adenoid hypertrophy(AH)with allergic rhinitis(AR)in the otitis media with effusion(OME)in children,as well as to discuss the risk factors on the inducement of OME in patients with AH.[Methods]The clinical materials were collected and analyzed from 205 children with AH who admitted for surgical treatment between 2013 and 2015, including medical history and signs,acoustic immittance measurement,allergy screen as well as blood routine,and to evaluate the situation of OME and AR in patients with AH. All the data were analyzed by SPSS 20.0.[Results]Among the 205 AH children,66 cases(32.20%)were accompanying with OME. The AH patients aged 3-5 years had the highest incidence of OME,which decreased with age(P=0.018). It is significant on the prevalence of the OME in patients with AH between the two groups with and without AR (P = 0.010). In the logistic model investigating the risk factors of inducing OME among patients with AH,the third-degree AH, Type-three and the accompanying with AR were significant. The third-degree and third-type AH children were 2.729 and 6.390-folds higher than others respectively (P = 0.047,P = 0.001). The incidence of OME appeared to be 1.212-folds higher among patients with AR(P = 0.010).[Conclusion]Mechanical obstruction and AR played a superimposed role in the inducement of OME among patients with AH,which was effected by multiple factors. We should pay attention to the“lateral respiratory”allergic diseases on eustachian tube and middle ear.

OBJECTIVE To obtain and compare the clinical characteristics in patients with allergic rhinitis(AR) and nonallergic rhinitis(NAR) and investigate the trends in the proportion of AR and NAR in recent 10 years in Guangzhou. METHODS 5486 patients with nasal hyper-reactivity symptoms were divided into the AR group and NAR group. Clinical data including gender, age distribution and seasonality were analyzed. RESULTS The trends in the proportion of AR and NAR during the past decade did not change significantly. Male made up the majority of AR patients and NAR patients and AR patients were significantly younger than NAR patients. Male AR patients were significantly younger than females, while there were no significant difference in the age distribution among the male NAR patients and female ones. As the age increasing, the proportion of AR and NAR patients in overall study population present opposite tendency. The main onset season in AR was summer and in NAR was winter in Guangzhou city. CONCLUSION There were significant differences between AR and NAR in age, gender and seasonality. However, the trends in the proportion of AR and NAR in recent 10 years did not change significantly in Guangzhou.

Objective To explore a variety of sustainable development under the network environment of doctor-patient communication service platform in the role of reproductive medicine nursing,to improve the reproductive efficiency of medical care services in the new environment,build new doctor-patient communication platform.Methods In reproductive medicine nursing practice,based on the internet to build diversification of doctor-patient communication information service platform,such as reproductive center website,QQ group of doctor-patient communication,Wechat public service platform.Through the questionnaire survey form,understand reproductive center patients through various network platform in the query,the information,make an appointment for reproductive assisted reproduction related information and interact with staff and other aspects of the usage and satisfaction.Results Recycling effective questionnaire was 517 papers.A total of the use of network platform for the overall coverage was more than 80％ of patients,among them the most widely Wechat public platform,utilization rate was 78.1％ (400/512);60.8％ (312/513) patients think Wechat platform using the most convenient.The overall satisfaction rate for center web services platform was 89.5％ (460/514).Conclusions Online platforms provide better nursing efficiency and quality,as well as improving doctor-patient communication based on the internet environment.It provides a new way for sustainable development for nursing system in the field of reproductive medicine.

Objective To investigate the early diagnostic value of serum Cystatin C in the diagnosis of acute kidney injury (AKI) in critically ill children.Methods Ninety-eight children of the severe case patients' rooms were divided into two groups:33 cases were AKI,65 cases were NAKI.Cystatin C and SCr in blood serum were detected by immunoturbidimetry and enzymic method every day.And compared serum Cystatin C,SCr concentrate and median diagnosis time between the two groups.Results Thirty-three cases in 98 cases of critically ill children occurred the AKI,65 patients without AKI.Comparing with the NAKI,the Cystatin C of AKI patients were significantly higher ((2.68 ±0.86) mg/L vs (0.76 ±0.15) mg/L) and SCr ((209.21 ± 100.53 ) μmol/L vs (77.46 ± 8.11) μmol/L),the differences were statistically significant (t =10.55,17.56,P ＜0.001) ; Cystatin C was in positive correlation with SCr (r =0.874,P ＜ 0.001) ; Median diagnosis time of AKI-Ⅰ,Ⅱ,and Ⅲ stage with Cystatin C were (3.0 ± 2.5) d,(5.0 ± 3.0) d and (9.0 ± 4.0) d,respectively,which was earlier than that of SCr ((5.0 ± 2.0) d,(7.0 ± 2.5) d and (10.0 ± 3.0) d,respectively; t =4.39,2.29,3.16,respectively ;P ＜ 0.01 or P ＜ 0.05).Conclusion In the process of AKI,the level of serum Cystatin C elevated significantly earlier than SCr,so it could as be one of the early dynamic criteria in the critically ill children.

BACKGROUND: In China, this laboratory is the first one to report such researches, confirming that strong αo-immunoreactive (IR) appears in the substantia gelatinosa (SG) of spinal cord and lateral spinal nucleus which is similar to the distribution of certain neuropeptides that participate in sensory regulation, which suggests that guanine nucleotide binding protein (G protein) may be related to primary afferent informational transfer. OBJECTIVE: To observe the change of αo-IR in gelatinous substance by the method of transection of unilateral spinal dorsal roots.DESIGN: A randomized controlled experiment on animals.SETTING: Staff Room of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiment was conducted at the Staff Room of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology from December 1995 to December 1996. Fifteen healthy adult SD rats were selected and divided into 3 groups: ①normal group with five rats (not dealt with any disposal), ②transected dorsal root group with 10 rats (right side) and ③control group (non-transected left sidedness as control).METHODS: Right lumbar 1-3 spinal neural dorsal roots were cut off under the anesthesia of 100 g/L chloral hydrate (300 mg/kg)through intraperitoneal injection in rats, living for 48-60 hours after operation. The subunit αo of guanine nucleotide-binding protein (rabbit polyclonal antiserum) was demonstrated in the αo-IR of rat spinal cord by immunohisto chemical methods. G protein was oriented, and its change was observed after transection ofneural dorsal roots MAIN OUTCOME MEASURES: ①The αo-IR of Ⅰ to Ⅲ of the dorsal horn and lateral spinal nucleus of the normal rats and control rats. ②The αo-IR of Ⅰ to Ⅲ of the dorsal horn and lateral spinal nucleus of rats in the transected dorsal root group. RESULTS: Data of a total of 15 rats were involved in the result analysis. ①In the normal group and control group, intense αo-IR was presented in rexed lamina ( Ⅰ to Ⅲ ) of the dorsal horn of rats, and the highest αo-IR in second lamina (SG). Lateral spinal nucleus of rat revealed higher density of αo-IR containing fiber networks. Following unilateral transection of dorsal roots in SG, αo-IR was markedly decreased. ②Quantitative analysis of absorbance (A) of αo-IR, it was (0.847±0.081) in the inside of the control group, (0.633±0.073)(t=5.71 ,P ＜ 0.001 ) in the inside of transected dorsal root group. It was (0.823±0.089) in the middle area of the control group,(0.660 4±0.074)(t=6.90,P ＜ 0.001 ) in the middle area of the transected dorsal root group. It was (0.915±0.090) in the lumbar region of the control group, and (0.656±0.077)(t=10.31 ,P ＜ 0.001 ) in the lumbar region of the transected dorsal root group. Average value of the control group was (0.852±0.084), and average value of the transected dorsal root group was (0.639±0.078)(t=10.23 ,P ＜ 0.001 ).CONCLUSION: Part of G protein of end-brush neurons related with the primary afferent noxious stimulation in SG derives from primary sensory neurons, which maybe join the adjustment of primary sensory transfer.