Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

In the treatment of diabetic gastroparesis(DGP),traditional Chinese medicine has conventionally focused on therapies such as ascending clear and descending turbid,pungent-opening and bitter-descending methods,aiming to regulate the ascending and descending of the spleen and stomach's Qi mechanism and to restore the middle-jiao's transformation as the ultimate goal.By explo-ring the physiological relationship between gallbladder and spleen-stomach and its pathological relationship with DGP,this article sug-gests that the gallbladder also participates in the regulation of blood sugar and digestive activities in the body,which is closely related to the onset of the disease.As the Shao Yang pivot,the gallbladder stores essential fluid,harbors ministerial fire,primarily governs the upward movement and dispersion,and is responsible for decision-making and emotions.The normal flow of Qi,blood,and body flu-ids,as well as the functional activities of the channels and collateral vessels,are closely associated with the gallbladder.When the gallbladder's function becomes abnormal,the body may also exhibit imbalances in the intestinal microbiota,disarray of gastrointestinal hormones,delayed gastric emptying,and elevated blood sugar levels,which aligns with the modern medical understanding of the onset of gastroparesis diabeticorum.Therefore,this article proposes the treatment principle of"venting the wood constraint"and the treatment of DGP according to symptoms,offering a reference for clinical treatment.

Objective:To evaluate the predictive value of baseline thyroid antibodies for thyroid adverse events following treatment with immune checkpoint inhibitors (ICIs) in malignant tumors using meta-analysis. Methods:Studies on the thyroid related adverse reactions following immune checkpoint inhibitor therapy for malignant tumors in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Literature was screened based on inclusion and exclusion criteria, study data were extracted, and meta-analysis was conducted using the RevMan 5.4 and Stata 12.0. Results:A total of 10 articles on ICIs therapy for malignant tumors were included, encompassing 1 480 patients, of whom 251 had positive baseline thyroid antibodies (TPOAb or TgAb). After ICIs therapy, 270 cases developed thyroid immune related adverse events (irAEs). Meta analysis showed that positive baseline thyroid antibodies predicted thyroid irAEs, with a pooled sensitivity of 0.45 (95% CI 0.35-0.56), pooled specificity of 0.95 (95% CI 0.91-0.98), pooled positive likelihood ratio of 4.04 (95% CI 3.01-5.42), pooled negative likelihood ratio of 0.57 (95% CI 0.48-0.68), and pooled diagnostic odds ratio of 16.31 (95% CI 9.76-27.24). The area under the summary receiver operating characteristics was 0.80 (95% CI 0.76-0.83). Meta regression showed that differences in regions and tumor types led to heterogeneity. Conclusion:Baseline thyroid antibodies (TPOAb and TgAb) have high predictive performance and specificity for thyroid irAEs after ICIs treatment of malignant tumors. This facilitates early prediction of thyroid irAEs, reduces the risk of adverse outcomes due to undiagnosed thyroid dysfunction, and holds important clinical value.

With the increase of global thyroid cancer (TC) incidence, it is imperative to assess these patients′ health-related quality of life (HRQoL). Due to the general good prognosis of TC, it is often considered a " good" cancer, but this impression overlooks the associated morbidity. In recent years, various studies have evaluated the HRQoL of TC patients. In this paper, the relevant factors of HRQoL in patients with TC are summarized, including surgery, radioactive iodine therapy and endocrine therapy, and the current assessment tools are also summarized to provide clinical reference.

Objective:To explore the effect of photobiomodulation (PBM) combined with umbilical cord mesenchymal stem cell transplantation on motor function recovery in rats with spinal cord injury.Methods:The mesenchymal stem cells were irradiated with a laser energy density of 1.5, 3, 6 and 12 J/cm 2. The optimal energy density was screened by the MTT method on the 3rd day. Before cell transplantation, 32 male SD rats were randomly divided into the spinal cord injury group, which was injected with normal saline without cells; the stem cell transplantation group, which was injected with stem cells in the injury model; the laser irradiation group, which was injected with cell-free saline and laser irradiation; and the combined treatment group, which was treated with cell transplantation and laser irradiation. BBB score and inclined plate test were performed on the 1st, 3rd, 7th, 14th and 21st day, and hematoxylin-eosin staining and Nissl staining were performed on the 21st day. Results:The laser irradiation with an energy density of 12 J/cm 2 can accelerate cell proliferation ( P<0.05). After the modeling, the BBB score of the combined treatment group was higher than that of the other groups (all P<0.05), and the motor function recovered significantly. In the inclined plate experiment, the performance of the combined treatment group and the laser irradiation group was also better than that of other groups. The results of hematoxylin-eosin staining showed that the cavity area in the combined treatment group was significantly reduced, and the inflammatory reaction was the lightest. The staining of Nissl bodies became deeper, and the spinal cord injury was significantly reduced. Conclusions:PBM can promote the recovery of motor function in rats with spinal cord injury after the transplantation of umbilical cord mesenchymal stem cells, and has an obvious therapeutic effect on spinal cord injury in rats. This study provides a basis for the treatment of spinal cord injury.

Background: Recent studies showed that the clinical outcome of moderately severe acute pancreatitis (MSAP) are different among different subgroups. Aims: To further subdivide MSAP, and explore the heterogeneity of MSAP subgroups. Methods: A retrospective analysis was performed on patients with acute pancreatitis (AP) from January 2016 to December 2020 at Northern Jiangsu People’s Hospital, including 538 patients with mild acute pancreatitis (MAP) and 461 patients with MSAP. MSAP patients were divided into four groups according to local complication and transient organ failure (TOF), including single acute peripancreatic fluid collection (APFC) without TOF group (group A), multiple APFC without TOF group (group B), other local complication without TOF group (group C) and TOF group (group D). The baseline data and the severity of AP among the four subgroups were compared. Meanwhile, the severity of disease between group A and MAP patients was also compared. Logistic regression analysis was used to evaluate the risk factors of MSAP. Results: Patients in group D were older than those in group A (P<0.05). There were statistically significant differences in different scoring systems among the four subgroups (P<0.05). The proportions of APACHE Ⅱ≥8, Glasgow≥3 and BISAP≥3 in group D were significantly higher than those in the other three groups (P<0.05). There were significant differences in levels of Ca

Acute pancreatitis (AP) is a common acute abdominal disease in clinical practice. As the hepatic manifestation of metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) is closely associated with the severity and prognosis of AP. This article elaborates on the mechanism of action of NAFLD in the development and progression of AP and further points out that NAFLD can induce AP and aggravate its severity through many ways.

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Objective To summarize the experience and effect of applying 3D printing to repair thoraco-abdominal aortic disease with fenestrated stent-graft or branch stent-graft technique.Methods From Oct 2017 to Sep 2018,22 patients with thoracic and abdominal aortic diseases,including aortic arterial dissection (9 patients) and aortic aneurysm (13 patients) were admitted.There were 19 males and 3 females,with mean age of (60 ± 13) years.Before the surgery 3D printing model guide plate was made according to CT,and then the pre-fenestrated stent-graft technique,branch stent-graft technique and other techniques were adopted in the surgery to perform endovascular repair.Resuits All of the operations were completed in one stage without open surgery.The average operation time was (5.67 ± l.23) hours without renal insufficiency and paraplegia,1 branch artery was lost during operation (1.4％) and 1 patient died (4.5％).Conclusion The application of 3D printing in the treatment of thoraco-abdominal aortic disease involving branches is more accurate than traditional measurement and localization.It had a safe and reliable short-term result.

Objective To investigate the value of standardized ultrasound screening in diagnosis of fetal congenital heart disease (CHD) during the first trimester. Methods This study retrospectively analyzed the clinical data of 8 383 fetuses who received ultrasound screening during the first trimester in the Dongguan Maternal and Child Health Hospital from September 2015 to December 2016. Standardized ultrasound was performed to observe fetal heart position, apical direction, apical four-chamber view, three vessels and trachea view and the thickness of nuchal translucency (NT). Fetuses with thickened NT or fetal CHD observed during the first and second trimester were followed up. Pregnancy outcomes and the growth of newborns within one year after birth were recorded and analyzed. Pathological results after the termination of pregnancy were compared with the results of routine karyotyping and chromosome microarray analysis (CMA). Results (1) A total of 27 cases of fetal CHD were identified during the first trimester giving a detection rate of 0.32% (27/8 383). These included ten (37.0%) of single atrium and/or single ventricle, seven (25.9%) of endocardial cushion defect (including two complicated by persistent arterial trunk), three (11.1%) of hypoplastic right heart syndrome, three (11.1%) of interventricular septal defect, two (7.4%) of hypoplastic left heart syndrome, one (3.7%) of mirror-image dextrocardia and one (3.7%) of right atrial enlargement and severe tricuspid regurgitation. Nineteen out of the 27 cases had NT thickening (NT≥3.0 mm) and 17 of them had a cystic hygroma (NT≥6.0 mm). Among the 27 cases, 22 were terminated in the first trimester which autopsy results were consistent with ultrasound and the other five were rescreened during the second trimester. Thirteen out of the 27 cases received chorionic villus sampling, and seven of them were found to have chromosomal abnormalities by karyotyping and CMA, among whom one was microdeletion of 22q11. (2) Twenty-one cases of CHD were detected in the second-trimester ultrasound screening, including five initially identified in the first trimester. These cases included four (19.0%) of complex cardiac malformations (with three or more malformations), four (19.0%) of interventricular septal defect, three (14.3%) of dextroaortic arch, left subclavian artery vagus and 'U' shaped vascular ring, three (14.3%) of hypoplastic right heart syndrome (including one complicated by coronary artery-right ventricular fistula and one by interventricular septal defect), two (9.5%) of transposition of the great arteries, two (9.5%) of tetralogy of Fallot, one (4.8%) of hypoplastic left heart syndrome, one (4.8%) of Taussig-Bing anomaly and one (4.8%) of coarctation of the aorta. Among the 16 cases first identified in the second trimester, eight had NT thickening, including one with cystic hygroma. Among the 21 cases, two were lost to follow-up after being transferred to another hospital; four with negative results in karyotype analysis and CMA were delivered vaginally at term (37-40 gestational weeks) with 1-min Apgar scores of ten points and postpartum ultrasound of the baby was consistent with the second-trimester ultrasound screening; 15 were terminated and the autopsy confirmed those findings in the second-trimester ultrasound screening. Eleven out of the 21 cases received amniocentesis and five of them were found to be abnormal according to karyotype analysis and CMA, including one of microdeletion of 22q11. Conclusions Standardized first-trimester ultrasound screening is important and of great clinical value in the diagnosis of fetal CHD. Increased NT thickness could be a key indicator of fetal CHD and chromosomal abnormalities in early pregnancy. CMA may facilitate detecting the abnormality of genetic material in fetuses with normal chromosome karyotype.