Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

With the rapid development of information technology,digitization of education has become an important driving force to promote education reform.In the education system of medical colleges,the construction and imple-mentation of professional curriculum courses play an important role in the cultivation of qualified medical talents.Emergence of education digitization has brought unprecedented opportunities but also some challenges to the curric-ulum construction by teachers in medical school.This paper aims to explore how to effectively promote construction of professional curriculums with information technology(IT)guided by education digitization strategy and to recom-mend a series of methods in terms of strategy implementation in medical schools.

Objective To evaluate the impact of lens capsule diameter and capsular tension ring(CTR)fit on the ro-tational stability and visual function of Toric intraocular lenses(IOLs)in patients with high myopia cataract after surgery,and to explore the main influencing factors.Methods A prospective study included 100 eyes of patients with high myopia(axial length≥26 mm)who underwent phacoemulsification cataract extraction combined with Toric IOL implantation at the Cataract Department of Hebei Eye Hospital from September 2023 to March 2024.Based on the ratio of the capsule equivalent diameter measured by anterior segment OCT(CASIA2)to the standard diameter of CTR,the eyes were divided into the matched group(ratio of 0.8-1.2)and the unmatched group.Follow-up was conducted at 1 week,1 month,3 months,6 months,and 12 months postoperatively to observe the rotation angle of Toric IOL,residual astigmatism,uncor-rected visual acuity,and other indicators.Safety was assessed based on intraoperative and postoperative complications.Correlation analysis and multiple linear regression were used to explore the impact of capsule-CTR fit,corneal astigmatism,axial length,and other factors on Toric IOL rotation and postoperative refractive status.Results The mean IOL rotation angle at each postoperative time point in the matched group was significantly smaller than that in the unmatched group,with statistically significant differences between groups at different time points(all P＜0.05).The matched group showed better stability in IOL decentration distance and tilt angle.At 12 months postoperatively,the residual astigmatism in the matched group was(0.53±0.29)D,which was better than that in the unmatched group(0.71±0.34)D(P=0.08).The matched group also had more significant improvement in uncorrected visual acuity and higher subjective visual quality scores.Multiple linear regression analysis showed that capsule-CTR fit and preoperative corneal astigmatism were the main independent factors affecting the rotation angle of Toric IOL(R2=0.52)and residual astigmatism(R2=0.46).Conclu-sion For patients with high myopia cataract,precise capsule-CTR matching based on CASIA2 measurement helps improve the rotational stability of Toric IOLs,reduce residual astigmatism,and enhance postoperative visual quality.Personalized CTR model selection is worth promoting and applying.

Objective To evaluate the impact of lens capsule diameter and capsular tension ring(CTR)fit on the ro-tational stability and visual function of Toric intraocular lenses(IOLs)in patients with high myopia cataract after surgery,and to explore the main influencing factors.Methods A prospective study included 100 eyes of patients with high myopia(axial length≥26 mm)who underwent phacoemulsification cataract extraction combined with Toric IOL implantation at the Cataract Department of Hebei Eye Hospital from September 2023 to March 2024.Based on the ratio of the capsule equivalent diameter measured by anterior segment OCT(CASIA2)to the standard diameter of CTR,the eyes were divided into the matched group(ratio of 0.8-1.2)and the unmatched group.Follow-up was conducted at 1 week,1 month,3 months,6 months,and 12 months postoperatively to observe the rotation angle of Toric IOL,residual astigmatism,uncor-rected visual acuity,and other indicators.Safety was assessed based on intraoperative and postoperative complications.Correlation analysis and multiple linear regression were used to explore the impact of capsule-CTR fit,corneal astigmatism,axial length,and other factors on Toric IOL rotation and postoperative refractive status.Results The mean IOL rotation angle at each postoperative time point in the matched group was significantly smaller than that in the unmatched group,with statistically significant differences between groups at different time points(all P＜0.05).The matched group showed better stability in IOL decentration distance and tilt angle.At 12 months postoperatively,the residual astigmatism in the matched group was(0.53±0.29)D,which was better than that in the unmatched group(0.71±0.34)D(P=0.08).The matched group also had more significant improvement in uncorrected visual acuity and higher subjective visual quality scores.Multiple linear regression analysis showed that capsule-CTR fit and preoperative corneal astigmatism were the main independent factors affecting the rotation angle of Toric IOL(R2=0.52)and residual astigmatism(R2=0.46).Conclu-sion For patients with high myopia cataract,precise capsule-CTR matching based on CASIA2 measurement helps improve the rotational stability of Toric IOLs,reduce residual astigmatism,and enhance postoperative visual quality.Personalized CTR model selection is worth promoting and applying.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Objective To investigate the role and primary mechanism of a novel fusion gene RELCH-RET in driving the malignant transformation of normal human bronchial epithelial(HBE)cells.Methods Based on retrospective clinical data from 456 non-small cell lung cancer(NSCLC)patients admitted in the Second Affiliated Hospital of Army Medical University from January 2019 to June 2022,a fusion gene,RELCH-RET,was identified as a research target.Three cell models were established:negative control(HBE VC,transfected with empty lentiviral vector),RET control(HBE RET,transfected with lentiviral overexpression vector of Flag-RET),and experimental group(HBE RELCH-RET,transfected with lentiviral overexpression vector of Flag-RELCH-RET).MTS assay and Transwell assay were used to detect cell proliferation and migratory and invasive abilities.In vivo tumorigenicity of the 3 cell models was assessed in 15 female non-obese diabetic/severe combined immunodeficiency(NOD/SCID)mice(SPF grade,4 weeks old,weighing 15.1±0.4 g)via subcutaneous xenograft experiments,with 5 animals in each group.Western blotting was employed to detect the autophosphorylation of RET(Y905)and the phosphorylation of downstream signaling proteins ERK1/2,EGFR(Y845)and STAT3(Y705).Dimerization and multimerization status of RELCH-RET were analyzed by chemical cross-linking(DTME treatment)in combination with Western blotting,with the reversibility being confirmed through de-cross-linking experiments.Results There were 3 cases carrying RELCH-RET fusion gene screened out from the 469 NSCLC patients.Compared with the HBE VC and HBE RET groups,the HBE RELCH-RET group exhibited significantly enhanced cell proliferation(P<0.01),and acquired migratory and invasive abilities(P<0.01),while the control groups did not demonstrate the abilities.In the mouse xenograft tumor model,HBE cells stably expressing RELCH-RET developed significant tumor nodules(P<0.001),whereas the control groups(empty vector and wild-type RET)failed to exhibit detectable tumor growth.Western blotting revealed that RELCH-RET could induce the autophosphorylation of the RET tyrosine residue(Y905)and significantly up-regulate the phosphorylation levels of ERK1/2,EGFR(Y845),and STAT3(Y705)proteins.Chemical cross-linking combined with Western blot analysis demonstrated that RELCH-RET formed a dimer(～170 kDa)in HBE cells,which is reversibly dissociated into monomers upon decross-linking treatment.Conclusion The novel fusion gene RELCH-RET,promotes ligand-independent dimerization/oligomerization,thereby mediating RET autophosphorylation,subsequently activates the downstream typical RET signaling pathway and ultimately drives the malignant transformation of normal HBE cells.

Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

Objective To optimize the extraction process of total phenolic acids from Cibotii rhizoma using Box-Behnken design-response surface methodology and evaluate antioxidant activity of total phenolic acid in vitro.Methods Taking the liquid-solid ratio,ethanol concentration and extraction temperature as influencing factors,and the extraction rate of total phenolic acids as evaluation indicator,the extraction process of total phenolic acids from Cibotii rhizoma was optimized using a three-factor and three-level Box-Behnken design-response surface methodology on the basis of single factor tests.Meanwhile,the scavenging effects of total phenolic acid extract from Cibotii rhizoma on ABTS·+and DPPH· was determined.Results The optimized extraction process for total phenolic acids from Cibotii rhizoma was as follows:the ethanol concentration of 55％,the extraction temperature of 88℃ and the liquid-solid ratio of 60∶1 mL/g.Under these conditions,the extraction rate could reach 8.67％.When the mass concentration of total phenolic acids extract were 2 mg/mL and 1 mg/mL,the clearance rates of ABTS·+and DPPH·were 92.76％and 88.66％,respectively.Conclusion The theoretical values obtained from the response surface optimization method are consistent with the actual measured values,and the extraction process of total phenolic acids from Cibotii rhizoma was simple and feasible.The total phenolic acids extract from Cibotii rhizoma exhibit strong antioxidant activity in vitro.