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 genetic diversity of Mycobacterium tuberculosis (MTB) in different types of tuberculosis and its association with clinical features, providing evidence for precise diagnosis and treatment of tuberculosis. Methods:This cross-sectional study included 103 cases of tuberculosis (38 with simple pulmonary tuberculosis, 43 with tuberculous pleurisy, and 22 with pulmonary combined with extrapulmonary tuberculosis) from Shenzhen Third People′s Hospital from 2015 to 2018. Paired bacterial strains from lung and pleural effusion/extrapulmonary sites were collected. Whole-genome sequencing (WGS) was used for drug resistance prediction, and genetic diversity (π value) was calculated as well as differential genes screening. Statistical analysis included paired t-tests and χ2 tests to compare clinical, bacteriological and genetic diversity features among groups.Results:The simple pulmonary tuberculosis group exhibited significantly higher rates of retreatment (71.7%, 27/38), cavitation (70.4%, 19/27), and multidrug-resistant or rifampicin-resistant (MDR/RR) (60.5%, 23/38) compared to the tuberculous pleurisy group (retreatment 11.9%, 5/42; cavitation 11.9%, 5/42; MDR/RR 16.3%, 7/43) and extrapulmonary tuberculosis group (retreatment 9.1%, 2/22; cavitation 18.2%, 4/22; MDR/RR 13.6%, 3/22) ( P<0.05). The overall π values of the MTB strain genomes in lung [(5.94±3.93)×10 ?5], pleural effusion[(6.22±3.51)×10 ?5], and extrapulmonary tissues [(5.83±3.54)×10 ?5] showed no significant differences ( H=0.10, P=0.94). Differential gene diversity analysis revealed that π value alternating genes related to respiration and intermediate metabolism were prominently high [tuberculous pleurisy 32.4% (11/34) and extrapulmonary tuberculosis groups 31.4% (32/102)], while cell wall-associated genes dominated in the simple pulmonary tuberculosis group (42.9%, 6/14). Drug resistance profiles and mutation spectra were identical across isolates from different sites within the same patient. Conclusion:WGS revealed the MTB diversity among different types of tuberculosis. Difference between pulmonary and extrapulmonary environments may impel the adaptive alternations of the bacterial strains to maintain survival with higher overall genome stability. Drug resistance testing of lung-derived isolates may provide references on extrapulmonary tuberculosis treatment.

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 genetic diversity of Mycobacterium tuberculosis (MTB) in different types of tuberculosis and its association with clinical features, providing evidence for precise diagnosis and treatment of tuberculosis. Methods:This cross-sectional study included 103 cases of tuberculosis (38 with simple pulmonary tuberculosis, 43 with tuberculous pleurisy, and 22 with pulmonary combined with extrapulmonary tuberculosis) from Shenzhen Third People′s Hospital from 2015 to 2018. Paired bacterial strains from lung and pleural effusion/extrapulmonary sites were collected. Whole-genome sequencing (WGS) was used for drug resistance prediction, and genetic diversity (π value) was calculated as well as differential genes screening. Statistical analysis included paired t-tests and χ2 tests to compare clinical, bacteriological and genetic diversity features among groups.Results:The simple pulmonary tuberculosis group exhibited significantly higher rates of retreatment (71.7%, 27/38), cavitation (70.4%, 19/27), and multidrug-resistant or rifampicin-resistant (MDR/RR) (60.5%, 23/38) compared to the tuberculous pleurisy group (retreatment 11.9%, 5/42; cavitation 11.9%, 5/42; MDR/RR 16.3%, 7/43) and extrapulmonary tuberculosis group (retreatment 9.1%, 2/22; cavitation 18.2%, 4/22; MDR/RR 13.6%, 3/22) ( P<0.05). The overall π values of the MTB strain genomes in lung [(5.94±3.93)×10 ?5], pleural effusion[(6.22±3.51)×10 ?5], and extrapulmonary tissues [(5.83±3.54)×10 ?5] showed no significant differences ( H=0.10, P=0.94). Differential gene diversity analysis revealed that π value alternating genes related to respiration and intermediate metabolism were prominently high [tuberculous pleurisy 32.4% (11/34) and extrapulmonary tuberculosis groups 31.4% (32/102)], while cell wall-associated genes dominated in the simple pulmonary tuberculosis group (42.9%, 6/14). Drug resistance profiles and mutation spectra were identical across isolates from different sites within the same patient. Conclusion:WGS revealed the MTB diversity among different types of tuberculosis. Difference between pulmonary and extrapulmonary environments may impel the adaptive alternations of the bacterial strains to maintain survival with higher overall genome stability. Drug resistance testing of lung-derived isolates may provide references on extrapulmonary tuberculosis treatment.

As global average carbon dioxide concentrations steadily rise,the frequency,intensity,and duration of cyanobacterial blooms in aquatic ecosystems are increasing annually.This phenomenon presents a significant threat to the overall health of global ecosystems and has garnered worldwide attention.In this study,an online detection of small-molecule dissolved gas concentrations in lake using a home-made membrane inlet mass spectrometer was conducted.Comparative water samples analyses demonstrated that the developed mass spectrometer instrument effectively discriminated between different water samples based on its dissolved gas detection capabilities.Online survey revealed that the concentrations of dissolved O2 and dissolved CO2 were 0.24 mmol/L and 1.31 μmol/L,respectively,in areas without cyanobacterial coverage.In areas with cyanobacterial coverage,their concentrations were 0.21 mmol/L and 0.92 μmol/L,respectively.In areas where cyanobacteria were densely collected,the dissolved CO2 content rose rapidly,while the dissolved O2 content decreased rapidly.This result revealed that large-scale cyanobacterial blooms exacerbated CO2 emissions,and during such blooms,lakes acted as sources of CO2,emitting substantial amounts into the atmosphere,thereby contributing to adverse impacts on global climate change.Furthermore,extensive cyanobacterial blooms led to a rapid decrease in dissolved O2 levels,resulting in O2 depletion and the mortality of fish and benthic invertebrates.The research highlighted the significance of the ratio of content of O2 and CO2 as a crucial indicator for cyanobacterial monitoring,with a smaller ratio indicating higher cyanobacterial content.Moreover,changes in turbidity and variations in the ratio of O2 and CO2 exhibited strong consistency.Large-scale algal blooms increased water turbidity,which posed a threat to the survival of aquatic organisms.This study provided a technological means for online detection of dissolved gases in water,offering essential references for water quality assessment,ecological evaluation,and particularly,for early prevention,mid-term management,and post-treatment effectiveness assessment of cyanobacterial blooms.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective:To explore the influencing factors and implementation paths of medical and preventive integration of chronic disease in county medical communities (CMCs), providing references for further promoting the integration of medical and prevention and improving the collaborative mechanism of medical and prevention.Methods:From October to November 2023, based on the principle of geographically balanced sampling, medical staff from 6 leading hospitals and 18 other member units of 6 CMCs in Zhejiang Province were selected as survey subjects. A self-designed survey questionnaire was conducted, mainly including the development and evaluation of chronic disease medical and preventive integration services in CMCs. The service development was designed according to the collaborative symbiosis management model, including 4 dimensions of collaborative symbiosis scenarios, willingness, ability, and process, as well as 11 secondary elements. Using secondary elements as the conditional variables and the integration effect of chronic disease medical and prevention as the outcome variable, a qualitative comparative analysis method was used to explore the relationship between multiple conditional variables and their combinations with high integration effect of chronic disease medical and prevention.Results:571 valid questionnaires were collected, with an effective response rate of 96.62%. The consistency of a single secondary element(including conditional non sets) on the high effectiveness of medical and preventive integration was less than 0.9, which cannot constitute a necessary condition for explaining the outcome variable. The configuration analysis results showed that the consistency of the condition combination formed by the interaction of multiple secondary elements was 0.835-0.845, indicating that the condition combination of multiple elements constituted a sufficient non necessary condition for the high integration effect of chronic disease medical and prevention. The configuration path for achieving high integration of medical and preventive effects could be divided into four categories, among which the feature of scenario-process dominance was to create a perfect service scenario and service process as the main focus; The characteristic of the willingness-process dominant type was to stimulate the service willingness of medical staff and improve the service process as the leading factor; The characteristic of the scenario-willingness-ability dominant type was to create a comprehensive service scenario, stimulate the service willingness of medical staff, and enhance service capabilities as the main focus; The characteristic of the willingness-ability-process dominant type was to stimulate the service willingness of medical staff, enhance service capabilities, and improve the service process as the dominant factor. In addition, the four types of configuration paths mentioned above all covered the two secondary elements of endogenous dynamics and professional competence, with a total coverage of 0.626 and a total consistency of 0.821.Conclusions:The configuration path formed through the interaction of multiple elements can effectively achieve the integration of chronic disease medical and prevention. The CMCs should choose the appropriate configuration path based on the actual situation. In addition, special attention should be paid to the endogenous motivation and professional capacity building of medical staff.

Early diagnosis of rheumatoid arthritis with the initiation of disease-modifying antirheumatic drugs is important to prevent future disability. Seronegative rheumatoid arthritis lacks the classical immunological markers, thus imposing clinical diagnostic difficulty. In this case, we reported 68 Ga-FAPI PET/CT findings of seronegative rheumatoid arthritis in a 60-year-old lady. This case illustrates how 68  Ga-FAPI PET/CT aids in the diagnosis of seronegative rheumatoid arthritis.

Metastasis from unknown primary is always a challenge because finding the true primary tumor significantly affects subsequent management. We present a case of malignant abdominal wall nodule initially diagnosed as metastasis from hepatocellular carcinoma through excisional biopsy and immunohistochemical (IHC) staining. Dual-tracer positron emission tomography/computed tomography (PET/CT) with 11 C-acetate and 18 F-FDG, however, showed metabolic findings in favor of metastasis from lung origin, which was finally confirmed by ensuing a lung biopsy with additional IHC stains. This case illustrates the complementary molecular role of PET to pathology, particularly when dual-tracer or multi-tracer PET is used in conjunction with pathology methods for cross referencing and confirmation.

AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P<0.05).CONCLUSION: The optimal concentrations for IHC staining in different proteins of mouse RP models were as follows: the concentrations of endoplasmic reticulum stress-related protein antibodies were 1:1000 in IRE1, 1:500 and 1:1000 in ATF6, 1:1500 in PERK, 1:200 in GRP78, and 1:100 in Caspase-12.