Computational analysis can accurately detect drug-gene interactions (DGIs) cost-effectively. However, transductive learning models are the hotspot to reveal the promising performance for unknown DGIs (both drugs and genes are present in the training model), without special attention to the unseen DGIs (both drugs and genes are absent in the training model). In view of this, this study, for the first time, proposed an inductive learning-based model for the precise identification of unseen DGIs. In our study, by integrating disease nodes to avoid data sparsity, a multi-relational drug-disease-gene (DDG) graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions. Following the extraction of graph features by utilizing graph embedding algorithms, our next step was the retrieval of the attributes of individual gene and drug nodes. In this way, a hybrid feature characterization was represented by integrating graph features and node attributes. Machine learning (ML) models were built, enabling the fulfillment of transductive predictions of unknown DGIs. To realize inductive learning, this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights, enabling inductive predictions for the unseen DGIs. Consequently, the final model was superior to existing models, with significant improvement in predicting both external unknown and unseen DGIs. The practical feasibility of our model was further confirmed through case study and molecular docking. In summary, this study establishes an efficient data-driven approach through the proposed modeling, suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Objective To explore the mechanism of methyltransferase METTL3 in premature ovarian failure(POF)using a POF mouse model,providing a theoretical basis for the pathological research and clinical treatment of POF.Methods C57BL/6 female mice aged 6 to 8 weeks were selected for the study.The experimental group consisted of mice with a premature ovarian failure(POF)model established using the D-galactose metabolic method,while the control group comprised normal mice subjected to the same intervention with an equal volume of physiological saline.The levels of sex hormones were measured using ELISA,and histopathological changes in ovarian tissue were observed through HE staining to verify the successful establishment of the POF mouse model and to explore the correlation between METTL3 and POF at the tissue level.Additionally,stable transgenic mouse granulosa cell lines with METTL3 overexpression and knockdown were constructed at the cellular level.Cell proliferation and apoptosis were assessed using CCK-8 and FITC/PI dual staining methods to clarify the regulatory role of METTL3 in granulosa cell apoptosis and its impact on the occurrence of POF.Results The POF mouse model was successfully established.TUNEL staining revealed a significant increase in apoptotic granulosa cells in the ovarian tissue of the POF group(P＜0.05),which also exhibited high expression of METTL3.In cellular experiments,stable transcriptional cell lines of mouse granulosa cells with METTL3 overexpression and knockdown were successfully constructed.Upregulation of METTL3 expression promoted granulosa cell apoptosis and inhibited their proliferation(P＜0.05).Conclusion METTL3 participates in the development of POF by promoting granulosa cell apoptosis.

N6-methyladenine(m6A)modification is involved in a variety of biological processes and dynamically regulates RNA stability.When m6A modification is changed,it affects the development of follicles,granulosa cell proliferation and oocyte development,and participates in the occurrence and development of benign ovaria-related diseases,such as polycystic ovary syndrome,premature ovarian dysfunction,and endometriosis,resulting in decreased female fertility.This article reviews the role and research progress of m6A modification in benign ovaria-related diseases,aiming to provide new diagnosis and treatment ideas for subsequent research on improving fertility.

Objective:To analyze the detection rate and related factors of depressive and anxious symptoms comorbidity in 2021 and 2022.Methods:Based on the results of the Seventh National Population Census in 2021,the residents of 32 provinces,municipalities,and autonomous regions were sampled by gender and age.The gender and age of the samples were in line with the characteristics of China's population.A face-to-face interview survey was conducted in community residents in each province in 2021(n=11 005)and 2022(n=30 421)with the Gen-eralized Anxiety Questionnaire-7 and Patient Health Questionnaire-9.Results:The detection rates of depressive and anxious symptoms comorbidity were 10.67％in 2021 and 11.72％in 2022.The prevalence of depressive and anxi-ety comorbidity were higher in male,younger(age≤17 years),divorced,lower BMI(BMI＜18.5 kg/m2),higher education(graduate),students,and residents with chronic medical history(Ps＜0.001).In 2022,32.06％of people with depressive symptoms had anxious symptoms and 47.62％of people with anxious symptoms had depressive symptoms.Conclusion:In 2021 and 2022,the detection rates of depressive and anxious symptoms comorbidity were both about 10％,and half of patients with anxious symptoms were accompanied by depressive symptoms,So atten-tion should be paid to the comorbidity of depression and anxiety symptoms.

Objective:To investigate the factors that contribute to acute lung injury(ALI)following thoracoscopic surgery in elderly patients with esophageal cancer.Methods:This study retrospectively analyzed the clinical data of 300 elderly patients with esophageal cancer who were treated in the hospital between June 2018 and June 2022.The baseline data of the patients were recorded and they were divided into two groups: ALI group and non-ALI group based on the postoperative complication of ALI.The study compared the baseline data of the two groups and used Logistic regression analysis to identify the influencing factors of ALI after thoracoscopic surgery in elderly patients with esophageal cancer.Results:This study involving 300 elderly patients with esophageal cancer found that 35 had ALI while 265 did not.Multiple Logistic regression analysis revealed that age increase( OR=1.573, P=0.031), a large number of lymph nodes cleaned( OR=3.145, P=0.008), and long tracheal intubation time( OR=1.108, P=0.028)were identified as risk factors for ALI in elderly esophageal cancer patients after thoracoscopic surgery.Conversely, high albumin levels were found to be a protective factor( OR=0.434, P=0.035). Conclusions:The incidence of acute lung injury(ALI)following thoracoscopic surgery in elderly patients with esophageal cancer is significantly high.Several factors contribute to this risk, including patient age, the number of lymph nodes cleaned, albumin level, and tracheal intubation time.

Objective:To investigate the antibacterial effect of iodophor on Staphylococcus aureus biofilm (BBF).Methods:Staphylococcus aureus were cultured in vitro and 480 pieces of titanium alloy plates were selected. On the surface of titanium plates, in vitro models of Staphylococcus aureus biofilms were established at days 7, 14, 21 and 28 respectively with 120 pieces of titanium plates at each time points. The biofilms at each time point were assigned to no iodophor immersion (PBS group), 5 g/L iodophor immersion for 5 minutes (5-min group) and 5 g/L iodophor immersion for 10 minutes (10-min group), according to the random number table method. FITC-ConA, propidium iodide (PI) and SYT09 were used to dye Staphylococcus aureus in PBS group. After dyeing, confocal laser scanning microscopy and scanning electron microscopy were used to observe the morphological structure of bacterial biofilms, and the Colony forming unit (CFU) was counted by the viable count method. In the other two groups, PI and SYT09 were applied to dye Staphylococcus aureus, and then confocal laser scanning microscopy and scanning electron microscopy were used to observe the changes of biofilms and bacterial viability after iodophor immersion. The antibacterial effect of iodophor was evaluated by the viable count method.Results:After dyeing Staphylococcus aureus with FITC-ConA and PI in PBS group, confocal laser scanning microscopy showed that the extracellular polymers of the bacteria increased gradually with the extension of culture time. The space structure of biofilm was gradually mature, changed significantly at day 21 and became mature at day 28. After staining Staphylococcus aureus with PI and SYT09 in PBS group, confocal laser scanning microscopy showed that the number of bacteria increased, and had a mountain-like shape. Scanning electron microscopy showed that the number of bacterial extracellular polymers increased gradually with the extension of culture time and a structured microenvironment was formed and gradually matured. In 5-min and 10-min groups, all bacteria were killed at days 7 and 14 [0(0, 0)CFU/ml], the antibacterial effect was weakened at 21 days, but the antibacterial effect of iodophor immersion in 10-min group [100 (100, 125)CFU/ml] was better than that in 5-min group [300 (275, 425)CFU/ml] ( P<0.05). There was no significant difference in iodophor immersion in 5-min group [500 (375, 700)CFU/ml] and 10-min group [250 (175, 400)CFU/ml] at 28 days ( P>0.05). Conclusions:The maturation of biofilm is the overall maturation of bacteria and bacterial extracellular polymers and the formation of a spatialized microenvironment. Bounded by the 21st day, biofilms are divided into young biofilms and mature biofilms. The main difference between them lies in the maturation of extracellular polymers and microenvironment. For the bacterial biofilm with culture time less than 21 days, the antibacterial effect of the iodophor immersion for 10 min is better than that of 5 min. However, for the bacterial biofilm with culture time greater than 21 days, there is no significant difference in the antibacterial effect of the bacterial biofilm of prolonged iodophor immersion time.

Objective: To investigate the effect of cough assist on sputum excretion and the outcome of withdrawal of mechanical ventilation after mechanically ventilated chronic obstructive pulmonary disease (COPD) patients with cough weakness. Methods: From January 2017 to December 2018, 74 patients with cough and weakness COPD after extubation of mechanical ventilation in the Department of Respiratory Critical Care Medicine of Hunan Provincial People's Hospital were divided into control group(n=37) and observation group (n=37) according to the random number table method. The patients in the control group were treated routinely after weaning and extubation, and the observation group was treated with cough assist after withdrawal of mechanical ventilation and extubation on the basis of the control group. The differences in drainage effect, blood gas index, reintubation rate and early prognosis index between the two groups were compared. Results: After the intervention treatment, the first active sputum excretion and the total sputum volume on the first day were (5.6±3.4) ml and (33.1±5.2) ml in the observationgroup, and (4.2 ±2.0) ml and (29.1±7.4) ml in the control group, the difference was statistically significant (t=-2.10, 2.875, P<0.05). The number of significant cases of respiratory sound improvement in the observation group and the control group was 21 and 14 cases, respectively, and the difference between the two groups was statistically significant (Z=-1.974, P < 0.05). The oxygen partial pressure (PaO₂) and oxygenation index (PaO₂/FiO₂) carbon dioxide partial pressure (PaCO₂) values of the observation group were (80.0±8.4), (345.9±19.2), (46.7±6.6)mmHg, and (74.8±9.1), (310.7±21.9), (50.9±7.1)mmHg in the control group. The difference was statistically significant (t=-2.504,-2.710, 2.579, all P<0.05). The reintubation rate, noninvasive ventilation time, and hospitalization days after the initial extubation in the observation group were as follows: 5.6%(2/36), (64.1±18.9)h, (6.0±1.7)d, and 22.2%(8/36), (76.7±15.3)h, (7.2±2.8)d in the control group. The difference was statistically significant (χ²=4.181, t=2.528, 2.438, all P<0.05). The non-invasive ventilation rate within 72h in the observation group and the control group were 63.9% (23/36) and 75.0% (27/36), the difference was not statistically significant (χ²=0.222, P>0.05). Conclusions The application of cough assist in RICU patients with cough weakness after extubation by mechanical ventilation can improve the expectoration efficiency of cough, improve oxygenation, reduce carbon dioxide retention, reduce the rate of re-intubation, shorten the time of noninvasive ventilation and hospitalization after extubation, and improve the curative effect.

Objective: To detect the expression of miR-133a-3p in gastric cancer (GC) tissues and plasma of GC patients, and to investigate its effect on the proliferation of GC cells as well as its correlation toprognosis of GC patients. Methods: 52 cases of cancertissues (non-necrosis part) and corresponding adjacent tissues as well as the pre-operative peripheral blood samples from GC patients, who underwent surgery at Department of General Surgery, the Forth Hospital of Hebei Medical University(Shijiazhuang, China) between May 2012 and May 2013, were collected for this study. The plasma sample (n=35) from healthy donors were obtained during their physical examination. RT-qPCR was adopted to detect the expression of miR-133a-3p in gastric cancer tissues, adjacent tissuesand plasma samples of GC patients and healthy volunteers. The relationships between miR-133a-3p expression and the median DFS as well as clinicopathological parameters were also analyzed. CCK-8 assay was adopted to detect the effect of miR-133a-3p silence or over-expression on proliferation of gastric cancer SGC7901 cells. Results: miR-133a-3p was dramatically decreased in gastric cancer tissues (P<0.01), and its expression was associated with TNM stage, tumor infiltration (T), lynphonode metastasis (N), and vascular tumor thrombus (all P<0.01); miR-133a-3p was significantly increased in the plasma of GC patients (P<0.01), and its expression was associated with TNM stage, lynphonode metastasis (N), and vascular tumor thrombus (all P<0.05). miR-133a-3p expression was positively correlated with serum CA199 level of GC patients (P<0.01). The median DFS of patients with high miR-133a-3pexpression in cancer tissues was significantly longer than that of the patients with low expression(20.8 vs 14.8 months, P<0.05); The median DFS of patients with high plasma miR-133a-3p expression was significantly shorter than that of the patients with low expression (14.4 vs 20.3 months, P<0.05). Over-expression of miR-133a-3p could significantly inhibit the proliferation of gastric cancer SGC7901 cells, while miR-133a-3p silence could significantly promote the proliferation (all P<0.05). Conclusion: miR-133a-3p could significantlyinhibit the proliferation of SGC7901 cells; miR-133a-3p aberrantlyexpressed in gastric cancer tissues and plasma, and obviously correlated with prognosis of gastric cancer patients, which may be used as a potential clinical bio-maker for early diagnosis and treatment as well as the prognosis prediction of gastric cancer.

Objective To observe the influence of renal sympathetic denervation (RSD) on renal interstitial fibrosis and transforming growth factor beta 1(TGF-β1) and microRNA-21 (miR-21) in rats with unilateral ureteral obstruction(UUO).Methods 40 male Wistar rats were randomly divided into UUO group (A group,n=10),sham UUO group (B group,n=10),RSD+UUO group (C group,n=1O) and RSD + sham UUO group (D group,n=10).Rats in A group and C group underwent unilateral ureteral ligation,while those in B group and D group underwent sham operation.Rats in C group and D group were followed by RSD.Rats were sacrificed at 21 days after the operation to evaluate the fibrosis by Masson staining.Immunohistochemical staining and Western blotting were used to detect the expressions of collagen I (COL-Ⅰ),collagen Ⅲ (COL-Ⅲ) and TGF-β1 in four groups.The expression of miR-21 was detected by fluorescence in situ hybridization (FISH) and quantitative real-time PCR (RT-qPCR).Results A large amount of collagen deposition was observed in the renal interstitial area in A and C group compared to either B or D group (P ＜ 0.05),but the change in C group was decreased significantly than that in A group (P ＜ 0.05).Similarly,the expressions of COL-Ⅰ,COL-Ⅲ,TGF-β1and miR-21 were obviously higher in A and C group compared to either B or D group (P ＜ 0.05),but those change in C group were decreased significantly than those in A group (P ＜ 0.05).The above indexes were not significantly different between B group and D group (P ＞ 0.05).Conclusion RSD may relieve the renal interstitial fibrosis in UUO rats,and down-regulate the expression of TGF-β1 and miR-21.

Objective: To investigate the safety, efficacy and prognostic factors of S-1 versus capecitabine in patients with advanced breast cancer (ABC). Methods: From January 1, 2012 to December 31, 2014, 154 ABC patients with pathological diagnosis were separated into two groups: S-1 with or without the 3rd generation chemotherapy drug (group S-1) and capecitabine with or without the 3rd generation chemotherapy drug (Group capecitabine). The efficacy, side effects and prognostic factors were compared between the two groups. Results: There were 70 patients in group S-1 and 84 patients in group capecitabine. The objective response rates (ORR) were 31.4% (22/70) in group S-1 and 28.6% (24/84) in group capecitabine. The disease control rates (DCR) were 74.3% (52/70) and 83.3% (70/84), respectively. There were no significant differences in DCR and ORR between two groups (P>0.05). The DCR of patients treated with capecitabine monotherapy was significantly higher than that of S-1 monotherapy [94.4%(17/18) and 64.0%(16/25), P=0.028]. The median PFS was 7.5 and 8.9 months for the patients in the group S-1 and group capecitabine, with no statistically significant difference (P=0.423). The 1-year survival rates of group S-1 and group capecitabine were 81.4% and 66.7%, respectively, with no significant differences(P=0.020). Univariate analysis showed that ER and/or PR status (P=0.004), T stage (P=0.041), and molecular typing (P=0.046) were associated with PFS. Multivariate analysis showed ER and/or PR status (P=0.034) was an independent prognostic factor related with PFS. The incidence of hemoglobin reduction was 14.3% (10/70) and 36.9% (31/84) in the group S-1 and group capecitabine, and the differences were statistically significant (P=0.002). There was no significant difference in the incidence of leukopenia, neutropenia, thrombocytopenia and hand-foot syndrome between the two groups(P>0.05). Conclusions S-1 and capecitabine are both effective for advanced breast cancer. Neither ORR nor DCR were significantly different between these two groups. The incidence of gastrointestinal reactions and thrombocytopenia of S-1 was slightly lower than that of capecitabine.