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.

Yang being solid is an important summary of the normal functional state of yang qi in The Yellow Emperor's Inner Classic.Based on the theory of yang being solid and able to hold on,it is proposed that yang being solid is essential to maintain the state of tightness,thoroughness and quietness for maintaining the health of the human body.Yang losing its solidity is the core patho-genesis of the onset and progression of malignant tumors,which manifests as yang deficiency,yang depression and yang restlessness.If yang is not solid due to its deficiency,yang will lose its warmth and defense and the evil qi will be retained;if yang is not solid due to its depression,yang will lose its warmth and circulation and phlegm and stasis will gather;if yang is not solid due to its restlessness,yang will lose its tranquility,burn yin and consume essence.Aiming at the core pathogenesis of yang losing its solidity,the treatment methods of warming yang and replenishing qi to treat the disease before it occurs,unblocking yang and removing turbidity to disperse the staleness,and clearing and resolving restless yang to fight cancer and detoxify are used in clinical practice.Restoring the solidity of yang is taken as the goal of treating malignant tumors,which provides ideas for the clinical practice of treating malignant tumors with traditional Chinese medicine.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.

Objective::This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor treatment immediately after percutaneous coronary intervention (PCI) on the myocardial salvage index (MSI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) 5-10 d after the procedure.Methods::The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention (PERFECT) trial is a prospective randomized controlled trial. From January 2021 to December 2023, 32 patients with anterior STEMI from Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial. Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group ( n = 16) or the control group ( n = 16), and their baseline data were collected. Patients in the PCSK9 inhibitor group (ie, alirocumab group) received a subcutaneous injection of PCSK9 inhibitor (alirocumab, 75 mg) immediately after PCI based on conventional treatment. In the control group, patients received only conventional treatment. The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI. The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T. Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period. Results::Baseline data during admission showed no intergroup significance. No significant difference in MSI (55.54% ± 14.80% vs. 44.72% ± 15.42%, P = 0.056) and left ventricular ejection fraction (51.24% ± 8.91% vs. 44.99% ± 8.84%, P = 0.060) was observed. Additional, there was no significant difference in the time to peak of creatine kinase isoenzyme-MB ((12.97 ± 5.67) h vs. (14.31 ± 7.04) h, P = 0.557) and high-sensitivity cardiac troponin T ((21.03 ± 12.46) h vs. (21.44 ± 9.99) h, P = 0.920) between the 2 groups. During the 6-month follow-up period, only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI. Conclusions::Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI. Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.

Objective::This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor treatment immediately after percutaneous coronary intervention (PCI) on the myocardial salvage index (MSI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) 5-10 d after the procedure.Methods::The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention (PERFECT) trial is a prospective randomized controlled trial. From January 2021 to December 2023, 32 patients with anterior STEMI from Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial. Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group ( n = 16) or the control group ( n = 16), and their baseline data were collected. Patients in the PCSK9 inhibitor group (ie, alirocumab group) received a subcutaneous injection of PCSK9 inhibitor (alirocumab, 75 mg) immediately after PCI based on conventional treatment. In the control group, patients received only conventional treatment. The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI. The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T. Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period. Results::Baseline data during admission showed no intergroup significance. No significant difference in MSI (55.54% ± 14.80% vs. 44.72% ± 15.42%, P = 0.056) and left ventricular ejection fraction (51.24% ± 8.91% vs. 44.99% ± 8.84%, P = 0.060) was observed. Additional, there was no significant difference in the time to peak of creatine kinase isoenzyme-MB ((12.97 ± 5.67) h vs. (14.31 ± 7.04) h, P = 0.557) and high-sensitivity cardiac troponin T ((21.03 ± 12.46) h vs. (21.44 ± 9.99) h, P = 0.920) between the 2 groups. During the 6-month follow-up period, only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI. Conclusions::Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI. Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.

Yang being solid is an important summary of the normal functional state of yang qi in The Yellow Emperor's Inner Classic.Based on the theory of yang being solid and able to hold on,it is proposed that yang being solid is essential to maintain the state of tightness,thoroughness and quietness for maintaining the health of the human body.Yang losing its solidity is the core patho-genesis of the onset and progression of malignant tumors,which manifests as yang deficiency,yang depression and yang restlessness.If yang is not solid due to its deficiency,yang will lose its warmth and defense and the evil qi will be retained;if yang is not solid due to its depression,yang will lose its warmth and circulation and phlegm and stasis will gather;if yang is not solid due to its restlessness,yang will lose its tranquility,burn yin and consume essence.Aiming at the core pathogenesis of yang losing its solidity,the treatment methods of warming yang and replenishing qi to treat the disease before it occurs,unblocking yang and removing turbidity to disperse the staleness,and clearing and resolving restless yang to fight cancer and detoxify are used in clinical practice.Restoring the solidity of yang is taken as the goal of treating malignant tumors,which provides ideas for the clinical practice of treating malignant tumors with traditional Chinese medicine.

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.