ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective This study aimed to compare the impacts of undertaking symmetrical bone repair of the nasal alar base combined with nasolabial deformity repair versus nasolabial deformity repair alone on the improvement in nasal de-formity of patients with unilateral cleft lip and alveolar cleft.Methods Fifty patients presenting with unilateral cleft lip and alveolar cleft were evaluated.Among them,20 underwent nasolabial deformity repair solely(non-bone grafting group),whereas 30 patients received bone repair in conjunction with nasolabial deformity repair(bone-repair group).Preoperative measurements and one-year follow-up results were assessed through photographic anthropometric analysis.According to the Farkas anthropometric standard,the nasal anatomic landmarks were located,and 10 nostril indicators were measured.The operative effects of two groups were compared.Results In contrast to the non-bone-grafting group,the nasal deformity of patients in the bone-repair group demonstrated significant improvement one year post-operation.The symmetry pa-rameters of the nasal columella more closely approximated 1,the columella deviation angle more closely approached 90°,and the sub-alare inclination angle and the inclination angle of the nasal alar were smaller(P＜0.05).Conclusion The accomplishment of symmetrical bone repair of the nasal alar base is conducive to enhancing nasal deformity after cleft-lip surgery in patients with unilateral cleft lip and alveolar cleft.This strategy has a positive influence on nasal symmetry,the morphology of the nasal alar,and nasal base deformity.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m 2 of Cisplatin and 30-40 mg/m 2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.

Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m 2 of Cisplatin and 30-40 mg/m 2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.

Objective To explore the impact of clinical treatment decisions on the long-term survival of different molecular subtypes of locally advanced breast cancer(LABC),and to promote the development of more effective and individualized treatment regimens for LABC.Methods The cases of LABC diagnosed by pathology from 2010 to 2015 were searched in the database.Breast cancer-specific survival(BCSS)and overall survival(OS)were estimated by plotting Kaplan-Meier curves.The log rank test(Mantel-Cox)was used to analyze the difference between the groups,and the benefit population of LABC was determined after for age,TNM stage,grade,treatment methods.Results The 5-year OS and BCSS were 77.43％and 84.34％in breast-conserving,and 68.03％and 76.90％in mastectomy,respectively.The 5-year OS and BCSS of Luminal A LABC were 79.91％and 87.23％in breast-conserving,and 71.78％and 81.16％in mastectomy,respectively.The 5-year OS and BCSS of Luminal B LABC were 79.30％and 83.14％in breast-conserving,and were 70.37％and 76.92％in mastectomy,respectively.The 5-year OS and BCSS of triple-negative LABC were 60.77％and 68.13％in breast-conserving,and those of mastectomy were 47.13％and 55.94％,respectively.The 5-year OS and BCSS of HER2 positive were 75.42％,82.05％in breast-conserving,and were 67.05％and 75.01％in mastectomy,respectively;The 5-year OS and BCSS of triple-positive LABC were 86.12％and 91.63％in breast-conserving,and 74.54％and 82.56％in mastectomy,respectively.The 5-year OS and BCSS of well differentiated and N0 triple-positive LABC patients with chemotherapy were 88.24％and 76.91％,and those of patients without chmotherapy were 88.24％and 90.91％,respectively(BCSS:P=0.812;OS:P=0.311).Conclusion In the selective population,OS and BCSS of patients with LABC undergoing breast conserving surgery were significantly better than those of mastectomy.When OS and BCSS were compared for different molecular types and stages of LABC,breast-conserving surgery was still superior to total mastectomy.LABC could be considered for highly differentiated,N0 stage Triple positive without chemotherapy.

Diabetic macular edema(DME)is the most common complication of diabetic retinopathy,which can cause vision loss in patients.The nosogenesis of DME is complicated,and about 1/3 DME patients have poor response to anti-vascular endothelial growth factor therapy,which is defined as refractory DME.The early identification of the risk factors of refractory DME is crucial and helpful for doctors to predict the prognosis of DME and guide clinical treatment.This arti-cle reviews the risk factors of refractory DME.

Objective:To analyze the influencing factors for depression in primary school children aged 9-10 years in Jiangsu Province, and to construct a risk prediction model.Methods:A retrospective study.A total of 1 162 primary school children aged 9-10 years from 3 primary schools in 3 regions of Jiangsu Province were recruited.Their demographic data were collected, and they were surveyed by the Depression Anxiety Stress Scales-21 (DASS-21), the Strengths and Difficulties Questionnaire (SDQ), and the Family Environment Scale (FES). Children were divided into control group (1 059 cases) and depression group (103 cases) based on the depression scores obtained from the DASS-21 scale.Multivariate Logistic regression analysis was used to analyze the influencing factors for depression in primary school students aged 9-10 and construct a risk prediction model. Results:There were significant differences in the economic development region, physical activities, academic performance, student cadres, parents′ education level, frequency of parental quarrels, SDQ and FES dimension scores between control group and depression group (all P<0.05). Among them, economic development areas (Northern Jiangsu and Southern Jiangsu), student cadres, father′s education level (elementary school and below) and intimacy of the FES scale were protective factors for depression in elementary school children; while emotional symptoms, peer problems and the total difficulty score in the SDQ scale, and the conflict in the FES scale were the risk factors for depression in elementary school children.The prediction model was created based on the influencing factors: Logit ( P)=-1.390×economic development area (Northern Jiangsu) -1.508×economic development area (Southern Jiangsu) -1.248×student cadres -2.206×father′s education level (primary school and below) -1.145×father′s education level (junior high school)+ 3.316×emotional symptoms in the SDQ+ 0.979×peer problems in the SDQ+ 2.520×total difficulty score in the SDQ -1.697×cohesion in the FES + 0.760×conflict in the FES -0.678.The area under the curve of receiver operating characteristic was 0.931, with the sensitivity and specificity of 85.42% and 91.83%, respectively. Conclusions:The regional level of economic development, class or school cadres, father′s education level, peer problems, total difficulty score, cohesion and conflict in the family are influencing factors for depression among primary school children aged 9-10 years in Jiangsu Province.The created prediction model can effectively assess the depressive risk factors in this population, which is conductive to achieve the early recognition and intervention of depression in them.