BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Epidemiological studies indicate that individuals with neurodegenerative diseases exhibit a comparatively lower risk of developing the majority of cancers.Although the precise mechanisms underlying this inverse correlation remain unclear,it is noteworthy that aberrant glucose metabolism,a pathological factor common to both conditions,may significantly contribute to this association.OBJECTIVE:To review the potential relationship between cancers and neurodegenerative diseases in glucose metabolism.METHODS:PubMed was searched for relevant literature using the search terms of"cancer,neurodegenerative diseases,Alzheimer's disease,Parkinson's disease,metabolic reprogramming,glucose metabolism,aerobic glycolysis,neuroprotection,aging,"and 136 articles were finally included for analysis.RESULTS AND CONCLUSION:Cancer and neurodegenerative diseases exhibit a profound pathological correlation at the level of glucose metabolism imbalance associated with aging.Cancer cells promote uncontrolled proliferation,invasion,and metastasis through the persistent activation of aerobic glycolysis,whereas neurodegenerative diseases are characterized by a reduction in aerobic glycolysis.Restoring aerobic glycolysis may confer neuroprotective effects and delay disease progression.The key nodes of glucose metabolism demonstrate a bidirectional regulatory pattern:metabolic regulators,which are significantly upregulated or aberrantly activated in cancer,are inhibited or functionally inactivated in neurodegenerative diseases.Mitochondria play a crucial role in mediating the aging process through the regulation of reactive oxygen species homeostasis and mitochondrial autophagy.They establish regulatory networks that connect cancer and neurodegenerative diseases,and maintaining their functional homeostasis is of paramount importance for disease prevention and treatment.

BACKGROUND:Due to the complex movement of the scapula,which is a six-degree-of-freedom activity in three-dimensional space,it is difficult to measure it accurately using traditional methods.The image and model matching technology based on dual-plane X-ray is a three-dimensional measurement method that has gradually developed and matured in recent years.Two high-speed cameras are used to project and shoot from orthogonal directions.Compared with a single perspective,this method has advantages in observation range and reduction of out-of-plane errors,and is suitable for the study of scapula kinematics.OBJECTIVE:X-ray biplane and image-model registration technology were used to explore the differences in scapular kinematics between normal individuals and patients with rotator cuff tears,providing a basis for the treatment and rehabilitation of rotator cuff tear patients.METHODS:From April 2023 to January 2024,10 patients with normal shoulders and 10 patients with rotator cuff tears who met the inclusion criteria were enrolled from Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The subjects underwent a shoulder CT scan to create a 3D model and a local scapular coordinate system.X-ray biplane images were taken during shoulder abduction with two C-arm machines.The 2D and 3D images were registered to compare scapular kinematic differences between the two groups at 0°,15°,30°,45°,60°,75°,and 90° of abduction,including scapular rotation angle and displacement distance.RESULTS AND CONCLUSION:(1)During shoulder abduction,the scapula of both groups showed upward rotation,but the upward rotation of the rotator cuff tear group was greater than that of the control group,and the difference was significant when the abduction was 30°-90°(P＜0.01).At the same time,the scapula internal rotation of both groups gradually increased,but the rotator cuff tear group was significantly greater than the control group when the abduction was 45°-90°(P＜0.01).In addition,the anteroposterior tilt of the scapula of the two groups was significantly different when the abduction was 15°-90°(P＜0.01).The scapula posterior tilt of the control group gradually increased during abduction,while the scapula of the rotator cuff tear group tilted forward except for a slight posterior tilt at 15°-30° abduction.(2)In terms of displacement,the upward displacement of the rotator cuff tear group was less than that of the control group during abduction,and the difference was significant at 15°-90°(P＜0.05),but there was no significant difference in lateral and anterior-posterior displacement between the two groups(P＞0.05).(3)Rotator cuff tear can cause scapular dyskinesis,characterized by increased upward rotation,internal rotation,and abnormal forward tilt during shoulder abduction.Identifying and addressing scapular dyskinesis is crucial for treating rotator cuff tear.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

To summarize the distribution characteristics of human papillomavirus(HPV) infection types in patients with cervical squamous intraepithelial lesion(SIL) and cervical cancer(CC), and to explore the impact of HPV vaccination, HPV infection types, and general clinical data on different grades of cervical lesions.

Objective: To explore the distribution characteristics and influencing factors of adverse reactions in whole blood donation in Jinan, Shandong, so as to provide evidence for the prevention and control of such adverse reactions in this region. Methods: A retrospective analysis was conducted on whole blood donors and adverse reaction cases in Jinan during 2023. To explore influencing factors of adverse reactions, univariate and multivariate logistic regression analyses were used to examine the relationships between adverse reactions and factors such as gender, age, donation organization mode, donation frequency, donation volume, time slot, and health examination results. Results: A total of 122 961 whole blood donations were recorded in Jinan in 2023. Donation-related adverse reactions occurred in 2 054 cases, with an incidence rate of 1.67%. Univariate analysis revealed significant differences in the incidence of adverse reactions across donor characteristics: the rate was higher in females (2.35%, 921/39 192) than in males (1.35%, 1 133/83 769), donors aged 18-25 years had the highest incidence (3.48%, 1 799/51 733), the incidence in group donations (3.13%, 1,737/55 534) was significantly higher than in individual donations (0.47%, 317/67 427), and insufficient blood collection was closely associated with adverse reactions (all P<0.001). Multivariate logistic regression analysis identified group donation, female gender, and a pulse rate of 81-99 beats per minute as risk factors for adverse reactions (all P<0.001), while systolic blood pressure of 116-139 mmHg and diastolic blood pressure of 76-89 mmHg were protective factors (all P<0.05). Compared to younger and lower-weight donor groups, older and higher-weight donors had a significantly lower risk of adverse reactions (all P<0.05). Donors giving 400 mL had a higher risk than those giving 200 mL (P<0.001). In addition, compared with the donation time slot of 7:00-8:59, the risk of adverse reactions was significantly higher during 9:00-16:59, with the time slot of 13:00-14:59 showing the most prominent risk (all P<0.05). However, no statistically significant difference was observed between the time slot of 17:00-20:59 and that of 7:00-8:59 (P>0.05). The primary clinical manifestation of adverse reactions was donation-related vasovagal reaction, with mental tension being the leading precipitating factor, accounting for 69.08% (1 419/2 054) of cases. Conclusion: The occurrence of adverse reactions in whole blood donation in the Jinan is influenced by multiple factors, including donor demographic characteristics, donation organization mode, physiological indicators, and time of donation. It is recommended to enhance the identification and intervention for high-risk groups, and optimize donation processes and service models to reduce the incidence of adverse reactions, thereby ensuring donor safety and blood quality.

This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.