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.

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

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.

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.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

Cibotii Rhizoma has a long history of folk usage and clinical applications,which is commonly used to treat symptoms such as waist and knee soreness,numbness of hands and feet.Its chemical components mainly include sugars and glycosides,aromatics,volatile oils,pterosins,flavonoids,steroids,pyranones,amino acids and inorganic elements.Pharmacological studies have shown that Cibotii Rhizoma has antioxidant,anti-inflammatory,anti-osteoporosis,gastrointestinal protection,antibacterial,liver protection,anticancer,analgesic and other effects.This paper systematically reviews the research status of chemical constituents,pharmacological effects and quality control of Cibotii Rhizoma,which provides reference for the development and rational use of Cibotii Rhizoma.

BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.

Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.