Objective To investigate the impact of dietary protein intake on the prevalence of type 2 diabetes in adult residents, and to provide a reference for formulating diabetes prevention and control measures. Methods The research was based on cross-sectional survey data from the Nutrition and Health Follow-up Study of Chinese Residents in Chongqing (2021). Energy and nutrient intake was calculated in combination with the Chinese food composition table. Multivariate logistic regression was used to analyze the association between dietary protein and diabetes, and then restricted cubic spline regression (RCS) was used to analyze the dose-response relationship between dietary protein intake and the development of diabetes. Results Among the 1 415 adult residents, dietary intake of total protein, animal protein, and plant protein was 69.69g/d, 26.26g/d, and 43.43g/d, respectively. The ratio of protein to energy supply was 14.31%, and the prevalence of diabetes was 18.02%. Comparing with the residents in the first percentile of total dietary protein intake, the multivariable-adjusted odds ratios of those in the second and third percentile were 1.754 and 2.453 respectively. Comparing the residents in the third percentile with those in the first percentile, the multivariable-adjusted odds ratios of diabetes were 1.592 for protein energy supply ratio, and 1.558 for animal protein intake. Conclusion High protein intake, high protein energy supply ratio and high animal protein intake may increase the risk of diabetes, and different types of protein may have different effects on diabetes.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

BACKGROUND:The healing of mandibular fractures after rigid internal fixation is influenced by many factors,including the material of the bone plate,fracture site,and bone density of the patient.However,there are relatively few studies on the relationship between the stability of mandibular fracture fixation in different bone qualities and they lack a scientific basis. OBJECTIVE:To analyze the stability of fixation of mandibular fractures with different bone qualities with bioabsorbable plates and miniature titanium plates by finite element analysis. METHODS:Three-dimensional finite element models of class Ⅰ-Ⅳ mandibular fractures were developed according to the bone quality classification method proposed by ZARB and LEKHOLM.The fractures at the median mandibular symphysis,mandibular body,and mandibular angle were simulated under different bone qualities.Bioabsorbable bone grafting plates(or miniature titanium plates)were placed at each fracture site for fixation and to simulate the state of healthy side occlusion.Finite element analysis on the model was used to analyze the relative displacement of the fracture segments and the stress distribution of fixators. RESULTS AND CONCLUSION:(1)The maximum stress value during fixation with titanium plates increased gradually with the increase of bone class,in which the maximum stress value of titanium plates was the highest in the mandibular body class Ⅳ bone group,which was 382.74 MPa and 96.11 MPa in the miniature titanium plate and bioabsorbable plate groups.The results for mandibles of the same bone type showed that the maximum stress value of titanium plates was much higher than that of bioabsorbable plates.(2)For fractures of the median middle of the mandible in types Ⅲ and Ⅳ,the displacement of the fracture breaks at the fixation site was large and exceeded the limiting value of bone healing(>150 μm),regardless of whether the fixation was performed with a miniature titanium plate or a bioabsorbable plate.For type Ⅳ mandibular fractures,the fracture end displacement in the bioabsorbable plate group exceeded the healing limit value,and the fracture end displacement in the miniature titanium plate group was close to the healing limit value.Under the same bone quality and fracture site,the fracture displacement of the miniature titanium plate group was smaller than that of the bioabsorbable plate group.(3)The results showed that the strength and stiffness of the two internal fixations were sufficient to support bone healing of fractures at three sites of the types Ⅰ-Ⅳ mandible,and the fixation stability of the bioabsorbable plate was almost the same as that of the miniature titanium plate,which could provide early healing conditions for fractures.Mandibular bone type should be taken into consideration in the treatment of mandibular fracture.The higher the mandibular bone grade,the worse the stability of fracture fixation,and the more likely the complications such as poor bone healing will occur after surgery.

BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear. OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

ObjectiveTo explore the potential mechanisms of Leigongteng （Tripterygium wilfordii Hook. f.） in treating rheumatoid arthritis （RA） using bioinformatics analysis and experimental validation. MethodsBioinformatics approaches， including the Gene Expression Omnibus （GEO）， the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Gene Ontology （GO） enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， protein-protein interaction （PPI） network analysis， molecular docking， receiver operating characteristic （ROC） analysis， and immune infiltration analysis， were used to predict the key active components of Leigongteng and its target genes for RA treatment. Experimental validation was conducted using human rheumatoid arthritis fibroblast-like synoviocytes （HFLS-RA） in vitro， with methotrexate as the positive control. A scratch assay was performed to assess cell migration after 24 hours of culture. Western blotting was used to detect protein expression levels， qPCR was used to measure target gene mRNA levels， and ELISA was conducted to evaluate inflammatory cytokine levels， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α）. ResultsA total of 117 target genes of Leigongteng were identified and intersected with RA-related genes， yielding 55 key genes. Further screening identified three core genes： PTGS2， CXCR4， and TIMP1. Based on the correspondence between potential drug targets and key components， triptolide and nobiletin were identified as the primary active compounds. Molecular docking results showed that both triptolide and nobiletin had binding energies lower than -5 kcal/mol with their respective target proteins， indicating strong interactions. In vitro experiments demonstrated that， compared with the blank control group， the triptolide， nobiletin， and positive control groups exhibited reduced cell migration rates after 24 hours of culture （P＜0.01）. The expression levels of PTGS2 and CXCR4 （both mRNA and protein） were significantly downregulated， while TIMP1 expression was upregulated. Levels of IL-1β， IL-6， and TNF-α decreased， whereas IL-10 levels increased （P＜0.01）. Compared with the positive control group， the triptolide and nobiletin groups showed increased cell migration rates， upregulated PTGS2 and CXCR4 expression （mRNA and protein）， downregulated TIMP1 expression （mRNA and protein）， increased IL-1β， IL-6， and TNF-α levels， and decreased IL-10 levels （P＜0.05 or P＜0.01）. ConclusionThe key active components of Leigongteng， triptolide and nobiletin， may alleviate RA by inhibiting PTGS2 and CXCR4 while promoting TIMP1 expression， thereby suppressing inflammatory responses.

Objective To explore the expression characteristics of BAIAP2L1 in cervical cancer (CC) and its regulatory role in tumor cell metastasis. Methods The correlation between BAIAP2L1 expression and clinical prognosis was analyzed by using a public database. GO pathway enrichment and clinicopathological correlation analyses were conducted by employing R language. The effect of BAIAP2L1 knockdown on CC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) were further investigated through gene silencing approaches. Results BAIAP2L1 expression was significantly upregulated in CC tissues (P_adj <0.001) and it was identified as an independent risk factor for patient mortality (HR=2.808, P=0.03). Elevated BAIAP2L1 levels showed significant correlations with poor overall survival, advanced T/N stage, recurrence, and metastasis (all P<0.05). Functional enrichment analysis revealed its involvement in tumor metastasis-related pathways. The knockdown of BAIAP2L1 significantly attenuated CC cell proliferation, invasion, and migration and suppressed key EMT processes (all P<0.05). Conclusion BAIAP2L1 is overexpressed in CC tissues and associated with patient prognosis and metastasis. The targeted inhibition of BAIAP2L1 can effectively curb tumor progression.

Objective To explore the effect of community pharmacy outpatient service on patients with type 2 diabetes mellitus. Methods A non-randomized controlled study was conducted, and type 2 diabetes patients managed in the community were divided into an intervention group of 112 cases and a control group of 110 cases. The control group received routine medication guidance during general practice outpatient visits, while the intervention group received comprehensive pharmacy outpatient service intervention based on routine medication guidance in general practice. Follow-up visits were conducted every 3 months. Repeated measurement analysis of variance and multivariate linear regression analysis were used to evaluate the intervention effect of the pharmacy outpatient service. Results Fasting blood glucose and glycosylated hemoglobin levels in the intervention group showed a decreasing trend with the increase of intervention time compared to pre-intervention time （P<0.01）, with increased duration of weekly exercise, decreased staple food intake, increased vegetable intake, and increased medication adherence score （P<0.01）. After adjusting for confounding factors through multivariate linear regression model, pharmacy outpatient intervention was found to be an independent protective factor for fasting blood glucose level （β=−0.891, P<0.01） and glycosylated hemoglobin level （β=−0.760, P<0.01） in the study subjects. Conclusion The community pharmacy outpatient service could enhance the self-management ability of patients with type 2 diabetes mellitus, and effectively improve patients’ fasting blood glucose and glycosylated hemoglobin.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

ObjectiveTo explore the main mechanism of self-precipitation formed during the decoction of Sinitang（SNT）， and to provide a research basis for exploring the differences in the toxic and effective components of this compound. MethodsThe average precipitation yields of SNT， Glycyrrhizae Radix et Rhizoma（GRR）-Aconiti Lateralis Radix Praeparata（ALRP） decoction（GF）， ALRP-Zingiberis Rhizoma（ZR） decoction（FJ）， GRR-ZR decoction（GJD）， ALRP decoction（FZ）， ZR decoction（GJ） and GRR decoction（GC） were determined. The four main self-precipitation samples of SNT， GF， FZ and GC were physically characterized by particle size， scanning electron microscopy（SEM）， pH， total dissolved solids（TDS）， conductivity， and Fourier transform infrared spectroscopy（FT-IR） analysis. The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） for SNT， SNT self-precipitation and SNT supernatant， and the contents of its main toxic and effective components were determined by high performance liquid chromatography（HPLC）. ResultsPrecipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield. The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes， and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation. A total of 110 components were identified in the SNT decoction， including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant. And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes， resulting in the following content hierarchy for free components：SNT decoctionsupernatantself-precipitation， these components included free liquiritin， benzoylmesaconine， benzoylaconitine， benzoylhypacoitine， liquiritigenin， aconitine， hypoaconitine， isoliquiritigenin and ammonium glycyrrhizinate. ConclusionSNT exhibits spontaneous precipitation during compound decoction， with GRR exerting the greatest influence on its formation. This suggests GRR plays a significant role in the detoxification of SNT. The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content， reflecting the characteristics of SNT "deposition in vitro and sustained release in vivo" and the importance of "administered at draught" in the clinical application of SNT.