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.

Endoplasmic reticulum stress(ERS)is associated with the pathophysiology of various lung diseases.Multiple experiments have confirmed that inhibiting ERS can alleviate inflammatory responses,improve lung function,and possess certain anti-infective effects.ERS inhibitors can positively impact the treatment of respiratory system diseases by targeting the unfolded protein response(UPR)in the ERS pathway and regulating the balance of calcium ions within the endoplasmic reticulum.Most current research on ERS inhibitors is still in the preclinical stage.This article thoroughly reviews the relevant reviews and various experimental research results on ERS in respiratory diseases,systematically examining the potential roles of the main branches of UPR,including inositol requiring enzyme 1 alpha(IRE 1α),protein kinase-like endoplasmic reticulum kinase(PERK),and activated transcription factor 6(ATF6),as well as other ERS inhibitors in respiratory diseases.The aim is to promote clinical trial exploration of ERS inhibitors,with the hope of providing effective drug selection strategies for the treatment and symptom relief of respiratory diseases.

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.

Endoplasmic reticulum stress(ERS)is associated with the pathophysiology of various lung diseases.Multiple experiments have confirmed that inhibiting ERS can alleviate inflammatory responses,improve lung function,and possess certain anti-infective effects.ERS inhibitors can positively impact the treatment of respiratory system diseases by targeting the unfolded protein response(UPR)in the ERS pathway and regulating the balance of calcium ions within the endoplasmic reticulum.Most current research on ERS inhibitors is still in the preclinical stage.This article thoroughly reviews the relevant reviews and various experimental research results on ERS in respiratory diseases,systematically examining the potential roles of the main branches of UPR,including inositol requiring enzyme 1 alpha(IRE 1α),protein kinase-like endoplasmic reticulum kinase(PERK),and activated transcription factor 6(ATF6),as well as other ERS inhibitors in respiratory diseases.The aim is to promote clinical trial exploration of ERS inhibitors,with the hope of providing effective drug selection strategies for the treatment and symptom relief of respiratory diseases.

Objective: To analyze the suicide attitude and influencing factors of college students with mental disorders in Shaoxing City, and to provide a basis for improving the attitude of college students with mentaldisorders towards suicide. Methods: From January 2018 to December 2021, 1 100 college students, among which 110 were previously confirmed by medical institutions to have mental disorders, were selected from two schools in Shaoxing, including Shaoxing University and Yuexiu Foreign Languages College, to participate in a questionnaire survey. Univariate and multivariate Logistic regression analysis were used to identify the main factors affecting the suicide attitude of college students with mental disorders. Results: Univariate analysis showed that the influence of different nature of college students with mental disorders on suicide attitude was related to age, gender, origin, suicide ideation, whether suicidal thoughts can be controlled, impulsive personality type, problem solving style, the differences were statistically significant ( χ 2/t=9.01, 15.05, 5.90, 5.86, 6.47, 4.92, 13.48, P <0.05). Multivariate Logistic regression analysis showed that age, gender, origin, suicidal ideation, uncontrolled suicidal thoughts, impulsive personality type, problem solving style were the main factors influencing the suicidal attitude of college students with mental disorders ( OR=3.13, 3.06, 2.89, 3.22, 3.25, 3.13 , 3.16, P <0.05). Conclusion problem solving and other factors. The selection of targeted treatment plan can improve the mental disorder condition of college students and promote the recovery of the disease.

Abstract: Objective To compare the application value of metagenomic next generation sequencing (mNGS) with traditional culture in diagnosis of pulmonary infection pathogens. Methods　The clinical documents of 310 patients with suspected pulmonary infection admitted to the General Hospital of Center Theater Command from February 2021 to September 2022 were retrospectively analyzed. The results of mNGS and traditional culture were analyzed, followed by comparison on the positive rate, sensitivity, specificity, accuracy (ACC), positive predictive value (PPV) and negative predictive value (NPV) between the two methods. Results　 The study revealed that mNGS can simultaneously detect multiple pathogens, with the highest efficiency of detection for bacteria and the lowest for fungi. And the sequencing numbers of bacteria, fungi and viruses shown by mNGS were significantly different (H=70.361, P<0.001). In comparison, mNGS displayed a higher positive detection rate (88.40%) than traditional culture (29.70%) (χ2=162.373, P<0.001), but the consistency between the two methods was not significant (Kappa = -0.003, P=0.902). The sensitivity, specificity, ACC, PPV and NPV of mNGS were 91.29%, 28.26%, 81.94%, 87.96%, and 36.11% respectively, compared to corresponding 30.30%, 73.91%, 36.77%, 86.96% and 15.60% of traditional culture respectively. Through analysis, it is confirmed that the sensitivity and specificity between the two methods were statistically significant (91.29% vs 30.30%, χ2=148.120, P<0.001 and 28.26% vs 73.91, χ2=13.793, P<0.001). Conclusions　mNGS can significantly improve the detection rate of pathogens in pulmonary infections and provide a complementary tool besides to traditional culture method for accurate anti-infection therapy. Furthermore, both traditional culture and mNGS pathogen detection methods are highly dependent on sample quality and detection quality control. mNGS requires the correct interpretation of comprehensive, non-destructive pathogenic genetic information to accurately identify pathogens.

Objective:To investigate the clinical characteristics and possible influencing factors of the extraintestinal manifestations (EIM) in patients with Crohn′s disease (CD) .Methods:Clinical data of 623 patients diagnosed as CD at Department of Gastroenterology, Shanghai Tenth People′s Hospital, from January 2008 to January 2018 were retrospectively analyzed. These patients were divided into two groups according to whether EIM was complicated. Univariate analysis was used to evaluate the clinical features, and multivariate analysis was used to reveal the risk factors of EIM. Fisher′s exact test was used to analyze the associations among various EIMs.Results:Among 623 CD patients, 422 (67.7%) were male and 201 (32.3%) were female; the median age at diagnosis was 31.0 years old (23.0 to 43.0 years old) ; the medium follow-up time was 53.5 months (29.0 to 84.0 months) . One hundred and twelve patients (18.0%) complicated with EIM, including 86 cases with one EIM, 22 case (19.6%) with two EIM, 3 case (2.7%) with three EIM, and 1 case (0.9%) with four EIMs simultaneously. Oral involvement was found in 84 cases (75.0%) , joints and bones in 36 cases (32.1%) , skin in 17 cases (15.2%) , and eye in 7 cases (6.3%) . Compared to patients without EIM, those with EIM had higher ratios of female (41.1% vs. 30.3%) , ileocolic (L3) type (52.7% vs. 37.6%) , non-stenosis and non-penetration (B1) type (69.6% vs. 54.2%) , diarrhea or fever as the first symptom (43.8% vs. 32.5%, 14.3% vs 6.5%) and steroids administration (53.6% vs. 39.3%) , while they had lower ratios of distal ileum (L1) type (19.6% vs. 36.8%) , stenosis (B2) type (26.8% vs. 37.0%) , penetration (B3) type (3.6% vs. 8.8%) , infliximab treatment (46.4% vs. 60.7%) , and abdominal surgery (14.3% vs. 24.1%) (all P<0.05) . Multivariate analysis showed that female ( OR = 1.665, 95% CI: 1.067-2.600, P = 0.025) , colonic type ( OR = 1.996, 95% CI: 1.072-3.718, P = 0.029) , ileocolic type ( OR = 2.568, 95% CI: 1.490-4.427, P = 0.001) , B1 type (B1 vs. B3: OR = 2.977, 95% CI: 1.015-8.726, P = 0.047; B1 vs. B2: OR = 1.882, 95% CI: 1.168-3.302, P = 0.009) and fever ( OR = 2.276, 95% CI: 1.170-4.430, P = 0.015) were the independent risk factors of EIM in CD patients. The oral lesion was significantly associated with spondylarthritis and skin diseases, and the spondylarthritis was closely associated with skin and eyes lesions (all P<0.05) . Conclusions:Female, colon involvement, B1 type and fever are the high risk factors of EIM for CD patients. Various EIM possess certain associations with each other.

Objective:To investigate the clinical characteristics and possible influencing factors of the extraintestinal manifestations (EIM) in patients with Crohn′s disease (CD) .Methods:Clinical data of 623 patients diagnosed as CD at Department of Gastroenterology, Shanghai Tenth People′s Hospital, from January 2008 to January 2018 were retrospectively analyzed. These patients were divided into two groups according to whether EIM was complicated. Univariate analysis was used to evaluate the clinical features, and multivariate analysis was used to reveal the risk factors of EIM. Fisher′s exact test was used to analyze the associations among various EIMs.Results:Among 623 CD patients, 422 (67.7%) were male and 201 (32.3%) were female; the median age at diagnosis was 31.0 years old (23.0 to 43.0 years old) ; the medium follow-up time was 53.5 months (29.0 to 84.0 months) . One hundred and twelve patients (18.0%) complicated with EIM, including 86 cases with one EIM, 22 case (19.6%) with two EIM, 3 case (2.7%) with three EIM, and 1 case (0.9%) with four EIMs simultaneously. Oral involvement was found in 84 cases (75.0%) , joints and bones in 36 cases (32.1%) , skin in 17 cases (15.2%) , and eye in 7 cases (6.3%) . Compared to patients without EIM, those with EIM had higher ratios of female (41.1% vs. 30.3%) , ileocolic (L3) type (52.7% vs. 37.6%) , non-stenosis and non-penetration (B1) type (69.6% vs. 54.2%) , diarrhea or fever as the first symptom (43.8% vs. 32.5%, 14.3% vs 6.5%) and steroids administration (53.6% vs. 39.3%) , while they had lower ratios of distal ileum (L1) type (19.6% vs. 36.8%) , stenosis (B2) type (26.8% vs. 37.0%) , penetration (B3) type (3.6% vs. 8.8%) , infliximab treatment (46.4% vs. 60.7%) , and abdominal surgery (14.3% vs. 24.1%) (all P<0.05) . Multivariate analysis showed that female ( OR = 1.665, 95% CI: 1.067-2.600, P = 0.025) , colonic type ( OR = 1.996, 95% CI: 1.072-3.718, P = 0.029) , ileocolic type ( OR = 2.568, 95% CI: 1.490-4.427, P = 0.001) , B1 type (B1 vs. B3: OR = 2.977, 95% CI: 1.015-8.726, P = 0.047; B1 vs. B2: OR = 1.882, 95% CI: 1.168-3.302, P = 0.009) and fever ( OR = 2.276, 95% CI: 1.170-4.430, P = 0.015) were the independent risk factors of EIM in CD patients. The oral lesion was significantly associated with spondylarthritis and skin diseases, and the spondylarthritis was closely associated with skin and eyes lesions (all P<0.05) . Conclusions:Female, colon involvement, B1 type and fever are the high risk factors of EIM for CD patients. Various EIM possess certain associations with each other.

Objectives: The purpose of this study is to summarize the historical experience of health financing in typical developed countries, in order to provide reference for China's health financing over the next 15 years.Methods: This paper uses hierarchical cluster analysis to determine the historical stage of typical developed countries similar to China in economic and social development from 2015 to 2030.Literature review is used to analyze the historical data and reform measures of health financing in typical developed countries during the similar stage.Results: The study found that the historical stage of typical developed countries that is similar to China in 2015-2030 is between the mid-or late-1970s and the beginning of the 21st century.During this period, the experience of health financing in typical developed countries mainly focused on controlling expenditures and costs, improving the health financing policy, strengthening the security system, etc.Conclusions: The similar stage research approach introduced in this paper provides a new idea and perspective to use the international experience for reference.Drawing lessons from the experience of health financing in typical developed countries combined with the Chinese context, this paper suggests the government should develop and improve diversified health financing channels, integrate and improve the health security system, and control the rapid escalation of health expenditure.

Objective:Based on the perspective of Universal Health Coverage(UHC),a mathematical model was developed to conduct quantitative study on the development status of Basic Medical Insurance Schemes(BMIS) in China.Methods:A mixed model was developed to conduct quantitative study on the development of BMIS in the period of 2003-2015 from five dimensions:coverage of population,benefit package,reimbursement rate,risk pooling level and unity of the schemes.Sensitivity analysis was also performed.Results:The UHC scores for BMIS in China from 2003 to 2015 fluctuated obviously.Given the range of 0-100 percent,the UHC score in 2003 was 52.2％,28.5％ in 2006,23.9％ in 2010 and 26.5％ in 2015.The integration and equalization of BMIS and scaling up the risk pooling levels were shown to contribute significantly to UHC.Conclusion:The construction of mixed models was developed to provide a new calculation assessment tool for measuring the UHC,which consisted of completed evaluation tool package with addition model and multiplication model.Considering the future development of UHC,there is a still long way to go for BMIS in China.Emphases should be given to integration and equalization of BMIS as well as scaling up the risk polling to provincial and national level.