BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

AIM:To explore the mechanism of Salvia miltiorrhiza(Danshen)-derived exosome-like nanoparti-cles(DDN)in attenuating oxidative damage in endothelial cells through the activation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/endothelial nitric oxide synthase(eNOS)signaling pathway.METHODS:The DDN were characterized by transmission electron microscopy and dynamic light scattering.Fluorescence microscopy and flow cytometry were used to evaluate the uptake of DDN by human umbilical vein endothelial cells(HUVECs).The viability,migration and invasion of HUVECs were assessed using CCK8 assay,wound-healing assay and Transwell assay,respec-tively.The HUVECs were induced by angiotensin II(Ang II)for oxidative stress and intervened with DDN or LY294002(a PI3K inhibitor).The levels of reactive oxygen species were determined by flow cytometry,and intracellular nitric oxide(NO)content was measured using a biochemical assay kit.Additionally,the protein levels of NADPH oxidase 4(NOX4),NOX2,endothelial nitric oxide syntnase(eNOS),p-eNOS,Akt and p-Akt were examined by Western blot.RESULTS:(1)Transmission electron microscopy and dynamic light scattering analysis revealed that DDN had good bio-compatibility and stability.(2)According to fluorescence images and flow cytometry results,DDN were strongly taken up by HUVECs.(3)Compared with control group,DDN significantly promoted the viability,migration and invasion of HUVECs,showing a dose-dependent effect.(4)Compared with control group,DDN remarkably increased intracellular NO levels,thereby enhancing endothelial cell vasodilation via activating the PI3K/Akt/eNOS signaling pathway.(5)The PI3K/Akt/eNOS pathway played a critical role in mitigating oxidative stress and improving cellular function in response to DDN treat-ment.CONCLUSION:The DDN mediate PI3K/Akt/eNOS signaling pathway activation to significantly alleviate Ang II-induced oxidative damage in endothelial cells,suggesting a potential vascular protective effect of DDN.

Objective To analyze the relationship between clinical drug utilization and the risk of nosocomial infections among hospitalized patients,and provide evidence for the prevention and control of nosocomial infections.Methods This study adopted a retrospective case-control design.The case group included 209 patients with nosocomial infection reported from January 2023 to December 2023 in a tertiary hospital.The control group included 209 patients without nosocomial infection during the same period.The patients in the control group were selected by stratified sampling based on Charlson Comorbidity Index(CCI).Results Univariate analysis showed that proton pump inhibitors,antacids,immunosuppressants and prior antimicrobial combination therapy increased the risk of nosocomial infection(P＜0.05).Multivariate log-binomial regression analysis showed that proton pump inhibitors,immunosuppressive drugs,and prior antimicrobial combination therapy were correlated with nosocomial infection.The corresponding relative risk(RR)was 1.31(95％CI:1.07-1.60),1.40(95％CI:1.02-1.91),and 1.66(95％CI:1.01-2.74),respectively.Further analysis indicated that the patients with nosocomial infection had longer time in use of proton pump inhibitors and prior antimicrobial combination therapy than the patients in the control group(Z=-6.331,P＜0.001;Z=-2.667,P=0.008).The trend Chi-square test showed that there was a dose-response relationship for proton pump inhibitors(x2=73.869,P＜0.001),immunosuppressive drugs(x2=16.530,P＜0.001),and prior antimicrobial combination therapy(x2=35.107,P＜0.001).Conclusions The use of immunosuppressants,proton pump inhibitors and antimicrobial combination therapy increases the risk of nosocomial infections in hospitalized patients.The prolonged use of these drugs will further increase the risk of nosocomial infection.

Objective To analyse phenotype and genetic variation of two congenital hypodysfibrinogenemia(Fg)caused by compound heterozygous variants and preliminary investigate their molecular pathogenic mechanisms.Metheds The proband A and B and their family members(a total of 19 members in 3 generations)who visited the First Hospital of Wenzhou Medical University on 4 May 2023 and 20 May 2023 for"parkinson's disease"and"pre-bilateral eyelid excision"were enrolled for the study.Prothrombin time(TT)and fibrinogen(Fg)activity were measured by coagulation assay and Fg antigen(Fg∶Ag)was measured by immunoturbidimetric assay for the two family members,and Fg aggregation assay was catalysed using human thrombin.FGG gene was amplified by PCR and se-quenced directly.The variant sites were analysed using Chromas software.Multiple sequence comparison was performed by ClustalX-2.1-win software.Pathogenicity analysis of the variant sites was performed using bioinformatics software.The analysis for FGG protein model was performed using PyMOL software.Results Phenotypic results showed TT of proband A and B extended to 27.5 s and 26.1 s,and plasma Fg activity reduced to 0.6 g/L and＜0.5 g/L,respectively.Genetic sequencing identified heterozygous c.1129+62_65delAATA on intron 8 of FGG gene in the both probands,resulting in the formation of aberrant amino acids at p.γGly377-Gly388 and an early ter-mination codon at p.γTyr389 site.A heterozygous missense variant c.103C＞A(p.AαArg35Ser)was found in exon 2 of the FGA gene of proband A,and a heterozygous missense variant c.569A＞G(p.BβAsn190Ser)was found in exon 4 of the FGB gene of proband B.Compared to the control group,the both probands showed significant decreases in peak and rate of Fg aggregation.Multiple sequence comparison analyses showed that all the three variant sites were conserved.Three bioinformatics software predicted both the missense variants were pathogenic.Protein modelling analysis showed that the number of hydrogen bonds in p.γGly377-Gly388 variant region was altered,resulting in steric hinderance.Conclusion All the two types of compound heterozygous variants,i.e.,c.1129+62_65delAATA and p.AαArg35Ser,c.1129+62_65delAATA and p.BβAsn190Ser,have been reported for the first time in Chi-na and worldwide to date,and the three variants may be related to the reduced Fg level and function in the two pedigree.

This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China,providing a reference for promoting enterprise R&D and production,as well as improving the supply guarantee mechanism for pediatric medicines.METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval,Pharnexcloud biomedical database,and National Medical Insurance Drug Directory,this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing.RESULTS As of June 30,2024,a total of 68 pediatric medicines had been approved through the priority review and approval process,covering 12 therapeutic areas,with oral dosage forms accounting for 64.71％.The median time from application to inclusion in priority review was 35.50 days,with an average of 41.69 days.The median time from inclusion in priority review to market approval was 1.24 years,with an average of 1.42 years.This included 12 domestic new medicines,21 domestic generic medicines,35 imported medicines,as well as 29 pediatric-specific medicines and 21 orphan medicines.Additionally,31 of these medicines had been included in the medical insurance catalog,representing a proportion of 45.59％.CONCLUSIONS Currently,a trend of differentiated competition is emerging between domestic and imported pediatric medicines.The therapeutic areas for pediatric medicines are continuously expanding,and the dosage forms are becoming more tailored to children's needs.However,there are still issues such as slow progress in new medicine development,insufficient stability in the medicine review and approval process,and a need to increase the proportion of medicines included in medical insurance.