Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore role of miR-146a in regulating TLR4/NF-κB pathway on inflammatory injury and neuropro-tection in intracerebral hemorrhage model rats and its possible mechanism.Methods:A total of 40 rats were selected and randomly divided into sham,model,over-expressing miR-146a adenovirus and negative virus injection groups,with 10 rats in each group.Garcia score was used for neurological function;HE staining was used to observe changes of brain tissues.ELISA was used to detect inflammatory factors levels.TLR4,NF-κB protein and gene expressions in brain tissues were detected by Western blot and RT-PCR.Results:Compared with model group,neural function score of overexpressed miR-146a adenovirus injection group was increased(P<0.05).Model group had abnormal cell morphology,edema and inflammation.Cell morphology,edema and inflammation were alleviated in overexpressed miR-146a adenovirus injection group.Inflammatory factors levels in model group were higher than sham group(P<0.05).Inflammatory factors levels in overexpressed miR-146a adenovirus injection group were lower than model group(P<0.05).TLR4,NF-κB protein and mRNA expressions in model group were increased than sham group(P<0.05).TLR4,NF-κB protein and mRNA expressions in overexpressed miR-146a adenovirus injection group were decreased than model group(P<0.05).Conclusion:miR-146a can improve neural function and reduce inflammatory injury in rats with intracerebral hemorrhage,possibly by inhibiting activation of TLR4/NF-κB signaling pathway and reducing inflammatory factors levels of brain tissues.

Objective To analyze the changes in the expression levels of serum Dickkopf-related protein 1(DKK-1)and latent transforming growth factor binding protein 2(LTBP2)in patients with connective tissue disease(CTD)related interstitial pneumonia(IP)of different disease activity levels before and after treatment.Methods A total of 121 CTD patients who visited the First Affiliated Hospital of Hebei North University from January 2022 to October 2023 were collected and separated into an observation group(CTD-related IP patients,n=62)and a reference group(CTD without IP patients,n=59)based on the incidence of IP.The observation group was separated into a stable phase group(n=26)and an acute exacerbation phase group(n=36)based on disease activity.Enzyme-linked immunosorbent assay(ELISA)detected DKK-1 and LTBP2 levels.Pearson or Spearman were used to analyze correlations between DKK-1 and LTBP2 levels with clinical data.Logistic regression was applied to analyze influencing factors of acute exacerbation in CTD-related IP patients.Results The serum levels of DKK-1(14.98±3.32 ng/ml)and LTBP2(32.64±4.01 ng/ml)in the observation group were higher than those in the reference group(2.21±0.67 ng/ml,8.73±2.15 ng/ml),the differences were statistically significant(t=28.983,57.518,all P＜0.05).The proportions of patients with ground glass opacity(66.67%)and honeycomb opacity(52.78%),serum DKK-1(19.67±4.10 ng/ml),LTBP2(38.76±4.92 ng/ml)and C-reactive protein(CRP)(32.46±3.12 mg/L)in the acute exacerbation group were higher than those in the stable phase group(30.77%,23.08%,8.48±1.37 ng/ml,24.17±3.65 ng/ml,22.05±2.80 mg/L),the differences were statistically significant(t/x2=7.790,5.534,13.362,12.781,13.524,all P<0.05).The serum levels of DKK-1 and LTBP2 in patients with acute exacerbation of CTD-related IP after treatment were positively correlated with ground glass opacities,honeycomb opacities,CRP and different disease activity(r=0.526,0.518,0.513,0.548;0.499,0.514,0.520,0.561,all P<0.05).As the treatment time extended,the serum levels of DKK-1 and LTBP2 in CTD-related IP patients in the stable and acute exacerbation groups decreased,and the serum levels of DKK-1 and LTBP2 in the acute exacerbation group were higher than those in the stable group before treatment,1 month after treatment,and 3 months after treatment,the differences were statistically significant(t=13.355,13.206,15.913;12.781,12.263,11.161,all P<0.05).DKK-1[OR(95%CI):2.458(1.297～4.657)],LTBP2[OR(95%CI):2.739(1.567～4.789)]were independent risk factors for acute exacerbation of CTD related IP patients(all P<0.05).Conclusion The serum levels of DKK-1 and LTBP2 in CTD-related IP patients are increased,and closely related to disease activity.Both decrease after 3 months of treatment and can monitor the treatment efficacy of patients to a certain extent.

Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.

Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.

Objective:To establish the quality evaluation method of Astmgali Radix based on three-dimensional fluorescence spectroscopy. Methods:The three-dimensional fluorescence spectra of Astmgali Radix extract was measured by fluorescence spectrum analysis technology, and the characteristics of fluorescence components of three-dimensional fluorescence spectrum of Astmgali Radix were analyzed by parallel factor analysis. The three-dimensional fluorescence spectra of Astmgali Radix samples from 23 different places were measured for quality discriminant analysis. Results:After the optimization, the three-dimensional fluorescence spectrum of 80% ethanol extract of Astmgali Radix showed that three groups of characteristic excitation/emission (λex/λem) peak, which located at 305 nm/420 nm (Peak 1), 280 nm/315 nm (Peak 2) and 265 nm/475 nm (Peak 3), respectively. The results of parallel factor analysis showed that Peak 1 and Peak 3 both contained one isoflavones fluorescent component, and Peak 2 contained two amino acid fluorescent components. There were differences in the number of characteristic peaks and fluorescence intensity of three-dimensional fluorescence spectra of Astmgali Radix samples from different origins. Conclusion:The three-dimensional fluorescence spectrum could evaluate the consistency of Astmgali Radix from different places. The method is simple, fast, and efficient. This method is accurate, which could provide reference for the quality evaluation of Astmgali Radix.

Objective: Screen the pathogenic genes of a pedigree with clinical manifestation of familial dilated cardiomyopathy in Inner Mongolia. Methods: A total of 3 patients with dilated cardiomyopathy and 20 family members from the same family were examined in Ordos Central Hospital in Inner Mongolia from October, 2003 to August, 2017. Data on medical history, physical examinations, electrocardiograms, and echocardiography were obtained. 5 ml peripheral blood was sampled for per person. Chip Capture Sequencing technology was used to capture all the exons and splice sites of the genes that associated with hereditary cardiomyopathy and hereditary arrhythmia. The mutations in these genes were detected by high-throughput sequencing. All suspected pathogenic loci identified by high-throughput sequencing were verified by Sanger sequencing used for mutation detection. One hundred and fifty gender, age and race matched healthy people were included as the control group. Results: Pathogenic gene variations were detected in 3 symptomatic family members and 1 carrier from the pedigree. Five pathogenic gene variations were identified in the proband (Ⅱ1), a pSer236Gly and a pArg215Cys variation in the MYBPC3 gene, a pGln90Arg variation in the DSP gene, and pAsn2912Asp and pGlu2910Val variation in the DMD gene. One pathogenic variation was detected in Ⅲ3, which was a pArg215Cys variation in the MYBPC3 gene. Two pathogenic variations were detected in Ⅲ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. Two pathogenic variations were detected in the Ⅳ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. No gene variation loci were detected in the other family members and the control group. Conclusion MYBPC3 gene, DSP gene and DMD gene variations are present in the familial dilated cardiomyopathy pedigree from Inner Mongolia, and these variations may be related with familial dilated cardiomyopathy.

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.

Liver cancer is a malignant tumor with the characteristics of high morbidity and mortality.However,the routine detection methods for the liver cancer such as imaging tests and pathological detection are with low specificity and sensitivity.And it's also hard to detect the condition of patients dynamically.Cell-free DNA (cfDNA) is the DNA fragment that is away from the extracellular and exists in the blood,which contains genetic information from the organism.The related disease information could be reflected on the cfDNA in patients with liver cancer,indicating that cfDNA has great potential in the screening,diagnosis,treatment and prognosis of liver cancer.The clinical applications of cfDNA can make up for the deficiency of existing detection methods and achieve noninvasive and dynamic monitoring of liver cancer.This article will present a review on the progress of clinical applications of cfDNA in liver cancer.