To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.

OBJECTIVE To investigate the application status of prescription pre-review systems in healthcare institutions of Yunnan province， evaluate their system functions and management capabilities， and provide a practical basis for promoting rational drug use. METHODS A questionnaire survey was conducted among public healthcare institutions at or above the secondary level in Yunnan province to investigate the deployment status of the systems. A capability maturity assessment framework was constructed， encompassing 6 dimensions and 39 indicators， including real-time prescription review， prescription correlation review， rule setting， evidence-based information support， prescription authority management， and system operation management. This framework was then used to evaluate the institutions that had implemented the pre-review systems. RESULTS A total of 100 valid questionnaires were collected， with 37 institutions having adopted prescription pre-review systems， mainly tertiary hospitals. The system predominantly adopted a modular architecture and was embedded into the hospital information system through application programming interfaces and middleware， providing certain capabilities for real-time prescription risk identification. Evaluation results indicated that basic functions such as reviewing indications， contraindications， and drug compatibility performed well， while deficiencies remained in functions related to parenteral nutrition prescription， review of drug dosage for specific diseases， individual patient characteristic recognition， and rule setting. Moreover， the construction of review centers and establishment of management systems were also not well-developed. CONCLUSIONS The overall application rate of prescription pre-review systems in Yunnan province remains low. System functions and management mechanisms require further improvement. It is recommended to enhance information infrastructure in lower-level institutions and explore regionally unified review models to promote standardized and intelligent development of prescription review practices.

Abelmoschi Corolla is extensively applied in managing diabetic nephropathy (DN) and other renal conditions due to its diuretic and detoxifying properties. The primary bioactive constituents of Abelmoschi Corolla are flavonoids, including notably rutin, hyperoside, isoquercitrin, hibifolin, myricetin, quercetin 3-O-β-D-glucuronide, and quercetin. These flavonoid components can influence the pathological progression of DN via a multi-target synergistic mechanism, effectively reducing proteinuria levels. This review examines the roles of Abelmoschi Corolla and its flavonoid components in modulating the key pathological aspects of DN and their underlying mechanisms, and briefly discusses the metabolic patterns of its bioactive components and the research progress in combined medication, aiming to provide a forward-looking scientific foundation for further investigating the molecular mechanisms and clinical applications of Abelmoschi Corolla in DN treatment.

ObjectiveTo investigate the therapeutic effect of sitravatinib on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice. MethodsA total of 30 male C57BL/6J mice， aged 8 weeks， were randomly divided into control group， CCl₄ model group， and low- （5 mg/kg）， middle- （10 mg/kg）， and high-dose （20 mg/kg） sitravatinib groups. All mice except those in the control group were given intraperitoneal injection of CCl₄ for 4 consecutive weeks to induce liver fibrosis， and since the first day of modeling， the mice in the low-， middle-， and high-dose sitravatinib groups were given sitravatinib at the corresponding dose by gavage every day. The serum levels of total cholesterol （TC）， triglyceride （TG）， and alanine aminotransferase （ALT） were measured for the mice in each group； hepatic hydroxyproline content was measured； HE staining， Masson staining， and Sirius Red staining were used to observe liver histopathological changes； quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of α-smooth muscle actin （α-SMA） and collagen type I alpha 1 （Col1a1） in liver tissue. The therapeutic effect of sitravatinib was assessed based on the above results. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had significant increases in the levels of TC， TG， and ALT （all P<0.05）， and there were no significant differences in the levels of TC， TG， and ALT between the model group and the low-， middle-， and high-dose sitravatinib groups （all P>0.05）. Hepatic hydroxyproline content decreased after sitravatinib intervention， with a significant difference between the middle-/high-dose sitravatinib groups and the CCl₄ model group （both P<0.05）. Histopathological staining showed that the sitravatinib treatment groups had a reduction in collagen deposition， along with thinning and fragmentation of fibrous septa， and in the high-dose sitravatinib group， 4 mice had a fibrosis stage of S0—S1 and 2 mice had a fibrosis stage of S2—S3， suggesting a certain degree of alleviation of liver fibrosis degree compared with the CCl₄ model group （mainly S3—S4）. The measurement of related molecules showed that sitravatinib downregulated the mRNA and protein expression levels of α-SMA and Col1a1 （all P<0.05）. ConclusionSitravatinib can effectively alleviate CCl₄-induced liver fibrosis in mice， possibly by inhibiting hepatic stellate cell activation and collagen synthesis.

BACKGROUND:One of the advantages of clear aligner treatment is molar distalization.However,tooth tilting movement and loss of anterior anchorage may occur during treatment.There are few studies on whether these problems can be improved by selecting clear aligners with different thicknesses and edges to improve the clinical treatment effect.OBJECTIVE:To analyze the control ability of clear aligners with different thickness and edges on the central incisor,lateral incisor,and second molar when pushing the maxillary second molar distally by three-dimensional finite element analysis.METHODS:Three-dimensional finite element analysis models of bilateral maxillary second molar distalization with clear aligner,maxillary dentition,periodontal ligament,and alveolar bone with different thicknesses and margins were established by Mimics,Geomagic Wrap,3-matic and SolidWorks software,respectively.There were 16 combinations of four thicknesses(0.4,0.5,0.625,and 0.75 mm)and four margins(scallop,straight,straight extension 2 mm and straight extension 4 mm).The data were imported into Ansys Workbench software for design and solution.The mean value,peak value and distribution of the periodontal ligament equivalent stress of the second molar,the equivalent stress and the maximum initial displacement of the second molar,and the control ability of each appliance on the second molar,central incisor,and lateral incisor were analyzed.RESULTS AND CONCLUSION:(1)The mean equivalent stress of periodontal ligament of the second molar,the equivalent stress of the second molar and the maximum initial displacement of the second molar increased with the extension of the appliance edge and the increase of the thickness of the appliance in the 16 groups of models.(2)When the thickness of appliances was the same,the maximum equivalent stress of the second molar in the linear appliance group was the highest,and the maximum equivalent stress of the second molar in the linear extended appliance group was greater than that in the scallop appliance group.When the edge of the appliance was the same,the periodontal ligament equivalent stress peak of the second molar increased with the increase of the thickness of the appliance.The equivalent stress distribution in the periodontal ligament of the second molar in the linear extendable appliance group was more uniform than that in the scallop appliance group and the linear appliance group.(3)When the thickness of the appliance was the same,the scallop-shaped appliance had the worst control on the second molar.When the edge of the appliance was the same,with the increase of the thickness of the appliance,the control of the second molar by the linear extender appliance was gradually stronger than that by the linear appliance.The control of the central incisor was stronger and more stable with the linear extended 2 mm appliance,while the control of the lateral incisor was stronger and more stable with the linear appliance.(4)The results showed that when using clear aligners to push molars distally,extending the edge of the appliance could improve the control of the molars and reduce the tilting movement of the teeth.The design of a straight extension margin of 2 mm for the central incisor and a straight edge for the lateral incisor can enhance the control of the anchorage incisor and reduce the labial inclination of the anterior teeth.

BACKGROUND:One of the advantages of clear aligner treatment is molar distalization.However,tooth tilting movement and loss of anterior anchorage may occur during treatment.There are few studies on whether these problems can be improved by selecting clear aligners with different thicknesses and edges to improve the clinical treatment effect.OBJECTIVE:To analyze the control ability of clear aligners with different thickness and edges on the central incisor,lateral incisor,and second molar when pushing the maxillary second molar distally by three-dimensional finite element analysis.METHODS:Three-dimensional finite element analysis models of bilateral maxillary second molar distalization with clear aligner,maxillary dentition,periodontal ligament,and alveolar bone with different thicknesses and margins were established by Mimics,Geomagic Wrap,3-matic and SolidWorks software,respectively.There were 16 combinations of four thicknesses(0.4,0.5,0.625,and 0.75 mm)and four margins(scallop,straight,straight extension 2 mm and straight extension 4 mm).The data were imported into Ansys Workbench software for design and solution.The mean value,peak value and distribution of the periodontal ligament equivalent stress of the second molar,the equivalent stress and the maximum initial displacement of the second molar,and the control ability of each appliance on the second molar,central incisor,and lateral incisor were analyzed.RESULTS AND CONCLUSION:(1)The mean equivalent stress of periodontal ligament of the second molar,the equivalent stress of the second molar and the maximum initial displacement of the second molar increased with the extension of the appliance edge and the increase of the thickness of the appliance in the 16 groups of models.(2)When the thickness of appliances was the same,the maximum equivalent stress of the second molar in the linear appliance group was the highest,and the maximum equivalent stress of the second molar in the linear extended appliance group was greater than that in the scallop appliance group.When the edge of the appliance was the same,the periodontal ligament equivalent stress peak of the second molar increased with the increase of the thickness of the appliance.The equivalent stress distribution in the periodontal ligament of the second molar in the linear extendable appliance group was more uniform than that in the scallop appliance group and the linear appliance group.(3)When the thickness of the appliance was the same,the scallop-shaped appliance had the worst control on the second molar.When the edge of the appliance was the same,with the increase of the thickness of the appliance,the control of the second molar by the linear extender appliance was gradually stronger than that by the linear appliance.The control of the central incisor was stronger and more stable with the linear extended 2 mm appliance,while the control of the lateral incisor was stronger and more stable with the linear appliance.(4)The results showed that when using clear aligners to push molars distally,extending the edge of the appliance could improve the control of the molars and reduce the tilting movement of the teeth.The design of a straight extension margin of 2 mm for the central incisor and a straight edge for the lateral incisor can enhance the control of the anchorage incisor and reduce the labial inclination of the anterior teeth.

Objective To develop models for predicting response to chemotherapy combined with immunotherapy in patients with esophageal squamous carcinoma with various machine learning algorithms,and then select the optimal model.Methods A retrospective study was performed for 174 patients with esophageal squamous cell carcinoma undergoing chemotherapy combined with immunotherapy admitted in Department of Thoracic Surgery of the First Affiliated Hospital of Army Medical University from January 2022 to December 2023.The CT scans and clinical information were collected before treatment.They were randomly divided into a training set(n=122)and a testing set(n=52)in a ratio of 7∶3.CT radiomic features were extracted and selected,and then 5 machine-learning algorithms were employed to establish the prediction models,including radiomics model and clinical-radiomics model.Five-fold cross-validation was conducted on the training set,and the performance of the prediction models was evaluated on the testing set using receiver operating characteristic(ROC)curve and the F1 score.The best-performing model was further explained using local interpretable model-agnostic explanations(LIME)algorithm.Results Among the 174 patients,115(66.1%)achieved clinical remission.From the clinical information and CT images,1 clinical features and 10 radiomic features were identified.The area under of ROC curve(AUC)for the radiomics and clinical-radiomics models was 0.750(95%CI:0.616～0.883),and 0.766(95%CI:0.637～0.895),respectively.The F1 score of the optimal clinical-radiomics model was 0.829.LIME algorithm indicated that this best model demonstrated reliability in predicting individual samples.Conclusion The clinical-radiomics prediction model based on machine learning algorithm performs well,and can provide a reference for doctors'clinical decision-making by predicting the response to chemotherapy combined with immunotherapy in patients with esophageal squamous cell carcinoma.

Objective To explore the potential role and underlying mechanism of the functionally uncharacterized gene Gm49394 on regulating β-cell apoptosis under diabetic conditions.Methods The expression and translational activity of Gm49394 in pancreatic β-cell lines and non-β-cell lines were validated using RNA fluorescence in situ hybridization(RNA-FISH),quantitative real-time PCR(qPCR),Western blotting,and immunofluorescence(IF)assay.The β-cell lines(NIT-1/Min6)with Gm49394 overexpression or knockdown were constructed.The proliferation,apoptosis,mitochondrial function,as well as oxidative stress and endoplasmic reticulum stress markers in these β-cell lines under physiological homeostasis or pathological stress conditions,such as high glucose(30 mmol/L),inflammation(10 ng/mL IFN-γ alone or combined with 10 ng/mL IL-6),and hydrogen peroxide(100 μmol/L H2O2)were detected by flow cytometry and Western blotting.Results RNA-FISH and qPCR indicated that Gm49394 was specifically expressed in pancreatic β-cell lines and up-regulated under high glucose or inflammatory stimulation.IF assay and Western blotting showed that Gm49394 had protein-coding activity.Flow cytometry and Western blotting identified that Gm49394 overexpression did not affect β-cell proliferation,but promoted β-cell apoptosis and increased reactive oxygen species(ROS)and mitochondrial superoxide(MitoSOX)levels in β cells under physiological homeostasis or pathological stress conditions(P<0.05).Under physiological conditions,Gm49394 knockdown failed to induce significant alterations on β-cell apoptosis,ROS,or MitoSOX levels.Under pathological stress conditions,Gm49394 knockdown significantly suppressed β-cell proliferation,apoptosis,as well as oxidative and endoplasmic reticulum stress(P<0.05).Conclusion Gm49394 may promote β-cell apoptosis via oxidative stress and endoplasmic reticulum stress.

Objective To investigate the protective effect of mitochondrial fission inhibitor 1(Mdivi-1),on organ function in rats with explosive blast injury combined with hemorrhagic shock.Methods A total of 192 SD rats(half male and half female,12 weeks old,weighing about 220 g)were randomly divided into 6 groups:Sham group(only surgical incision along the midline of the abdomen),model group(ESH group,thermal radiation and shock wave injury followed by femoral artery hemorrhage),lactated Ringer's solution resuscitation group(ESH+LR group,LR solution infusion in the femoral vein for resuscitation),and low-,middle-and high-dose Mdivi-1 groups(0.1,0.5 and 1.0 mg/kg Mdivi-1 intervention after infusion of LR solution).Fluorescent protein tracing was used to determine the leakage amount of fluorescent protein in the lung and kidney tissues to evaluate the vascular permeability.Evans blue dye staining was employed to observe the intestinal permeability and pulmonary vascular permeability.Laser Doppler flowmetry was applied to monitor the tissue blood perfusion in the liver,kidneys,and intestine.Serum levels of cardiac injury marker troponin I(TNI),liver function markers aspartate aminotransferase(AST)and alanine aminotransferase(ALT),and renal function markers serum creatinine(Scr)and blood urea nitrogen(BUN)were detected to evaluate the functions of corresponding organs.The water contents of the lungs and brain were calculated by measuring wet weight and dry weight of the lung and brain tissues.Blood pressure,heart rate,and respiratory rate were monitored.The survival time and 72-hour survival rate were recorded and calculated.Results Compared with the Sham group,the ESH group exhibited significantly increased vascular permeability in the lungs and kidneys as well as intestinal tissue(P<0.05),along with obviously elevated water contents in the lungs and brain(P<0.05),and decreased blood perfusion in the liver,kidneys,and intestine by 57.1%,39.2%,and 43.2%of the Sham group,respectively(P<0.05),elevated levels of TNI,AST,ALT,Scr and BUN(P<0.05),mean survival time of 3.8±1.1 h,and a 72-hour survival rate of 0(P<0.05).Although LR solution resuscitation reduced vascular permeability and alleviated organ injury in rats with explosive injury combined with hemorrhagic shock,there were no significant differences compared to the ESH group(P>0.05).Mdivi-1 treatment notably decreased vascular permeability in the lungs and kidneys and intestine,and water contents in the lungs and brain when compared with the LR group(P<0.05),with the dose of 0.5 mg/kg demonstrating the most significant effect.Additionally,Mdivi-1 treatment also significantly enhanced organ perfusion,improved organ functions,prolonged survival time,and increased survival rate.The 0.5 mg/kg treatment resulted in a 72-hour average survival time 55.64 h and a survival rate of 62.5%.Conclusion Mitochondrial fission inhibitor Mdivi-1 can reduce the permeabilities in the lungs,kidneys and intestine,improve tissue blood perfusion,protect the organ functions of the heart,liver and kidneys,and finally prolong survival time and increase survival rate in rats with concomitant explosive blast injury and hemorrhagic shock.

″Boundarics in biomedicine″(or″Biomedical boundarics″)is an emerging frontier interdisciplinary subject that focuses on addressing key scientific issues related to the formation,identification,and evolution of biological boundaries within living organisms.In this field,the study of tumor boundaries is of particular importance.Imaging tumor boundaries not only helps to reveal the molecular mechanisms of tumor boundary evolution and interaction with the microenvironment,tumor invasion and metastasis,but is also crucial for clinical tumor diagnosis,treatment decision-making,efficacy monitoring and prognosis evaluation.Molecular probes,as functional substances that enhance imaging signals,play a crucial role in tumor boundary recognition.In this article,the basic concepts and research significance of boundarics in biomedicine and tumor boundarics in biomedicine were summarized firstly.Then a comprehensive review of the research progress in tumor boundary imaging molecular probes was provided,covering areas such as magnetic imaging,optical imaging,acoustic imaging,nuclear imaging,and multimodal imaging.The strategies to regulate the sensitivity,specificity,and safety of molecular probes through chemical structure modifications,conjugation with targeting ligands,and tumor microenvironment-responsive designs were emphasized.Finally,the research trends of molecular probes for tumor boundary imaging were analyzed,and the challenges faced in this field and the future research directions were discussed.