Objective To explore the factors influencing blood drug concentrations of first-line anti-tuberculosis drugs in fixed-dose combinations by analyzing therapeutic drug monitoring data from tuberculosis patients receiving these regimens.Methods This retrospective study enrolled 224 patients who received treatment at Guangzhou Chest Hospital between January 2020 and December 2024.All participants underwent standardized therapy during the intensive phase,with therapeutic drug monitoring of first-line anti-tuberculosis drugs(ANTDs),including isoniazid(INH)and rifampicin(RFP).Data collection was completed in January 2025,at which time clinical records and measured INH and RFP plasma concentrations were updated.Data analysis was conducted from January to February 2025.Eight baseline variables—gender,age,hypoproteinemia(serum albumin<35 g/L),glomerular filtration rate(GFR),and others—were collected.Univariate chi-square tests and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic INH and RFP plasma concentrations.Results Among the study participants,71.43%(160/224)exhibited blood drug concentrations below the reference range for INH,compared to 41.07%(92/224)for RFP.The mean blood concentrations(mg/L,±SD)were 2.532±1.371 for INH and 9.428±4.317 for RFP,respectively.One-way analysis indicated significant associations between male gender,positive etiological test results,and subtherapeutic RFP concentrations(P<0.05),suggesting statistically significant differences.Multivariate regression analysis further revealed that male gender(OR=1.992,95%CI:1.094～3.628)and positive etiological tests(OR=1.929,95%CI:1.058～3.517)were independent risk factors for low RFP levels.Conclusions This study demonstrates that therapeutic drug monitoring(TDM)frequently identifies subtherapeutic RFP concentrations in tuberculosis patients undergoing treatment.Multivariate analysis reveals that male sex and positive pathogen test results are independent risk factors associated with low RFP plasma levels.Consequently,clinicians should exercise heightened vigilance in patients exhibiting these characteristics,promptly implementing TDM to guide individualized dose adjustments.Such an approach is crucial for optimizing treatment efficacy and minimizing the risk of drug resistance development.

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Objective To explore the factors influencing blood drug concentrations of first-line anti-tuberculosis drugs in fixed-dose combinations by analyzing therapeutic drug monitoring data from tuberculosis patients receiving these regimens.Methods This retrospective study enrolled 224 patients who received treatment at Guangzhou Chest Hospital between January 2020 and December 2024.All participants underwent standardized therapy during the intensive phase,with therapeutic drug monitoring of first-line anti-tuberculosis drugs(ANTDs),including isoniazid(INH)and rifampicin(RFP).Data collection was completed in January 2025,at which time clinical records and measured INH and RFP plasma concentrations were updated.Data analysis was conducted from January to February 2025.Eight baseline variables—gender,age,hypoproteinemia(serum albumin<35 g/L),glomerular filtration rate(GFR),and others—were collected.Univariate chi-square tests and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic INH and RFP plasma concentrations.Results Among the study participants,71.43%(160/224)exhibited blood drug concentrations below the reference range for INH,compared to 41.07%(92/224)for RFP.The mean blood concentrations(mg/L,±SD)were 2.532±1.371 for INH and 9.428±4.317 for RFP,respectively.One-way analysis indicated significant associations between male gender,positive etiological test results,and subtherapeutic RFP concentrations(P<0.05),suggesting statistically significant differences.Multivariate regression analysis further revealed that male gender(OR=1.992,95%CI:1.094～3.628)and positive etiological tests(OR=1.929,95%CI:1.058～3.517)were independent risk factors for low RFP levels.Conclusions This study demonstrates that therapeutic drug monitoring(TDM)frequently identifies subtherapeutic RFP concentrations in tuberculosis patients undergoing treatment.Multivariate analysis reveals that male sex and positive pathogen test results are independent risk factors associated with low RFP plasma levels.Consequently,clinicians should exercise heightened vigilance in patients exhibiting these characteristics,promptly implementing TDM to guide individualized dose adjustments.Such an approach is crucial for optimizing treatment efficacy and minimizing the risk of drug resistance development.

Background/Aims: Previous studies have shown that diet and physical activity can influence constipation. However, the combined effect of diet and physical activity on constipation remains unclear. Methods: Constipation was defined based on stool consistency and frequency, while overall diet quality was assessed using Healthy Eating Index (HEI)-2015 scores. Participants were categorized into low (metabolic equivalent [MET]-min/wk < 500) and high physical activitygroups (MET-min/wk ≥ 500). The association between diet and constipation across physical activity groups was analyzed using surveylogistic regression and restricted cubic splines. Results: Higher HEI-2015 scores were associated with reduced constipation risk in the high physical activity group when constipation was defined by stool consistency (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99). However, in the low physical activity group, increased HEI-2015 scores did not significantly affect constipation risk (OR, 1.01; 95% CI, 0.97-1.05). Similar results were found when constipation was defined based on stool frequency. In the high physical activity group, increased HEI-2015 scores were significantly associated with a reduced constipation risk (OR, 0.96; 95% CI, 0.94-0.98). Conversely, in the low physical activity group, increased HEI-2015 scores did not affect the risk of constipation (OR, 0.96; 95% CI, 0.90-1.03). Conclusions Our findings suggest that a higher HEI-2015 score is negatively associated with constipation among individuals with high physical activity levels but not among those with low physical activity levels. This association was consistent when different definitions of constipation were used. These results highlight the importance of combining healthy diet with regular physical activity to alleviate constipation.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective:To investigate the isolation characteristics and the antibiotic resistance of Streptococcus pneumoniae in hospitalized children from the Bao′an District of Shenzhen for many consecutive years, and to provide evidence for the assessment as well as clinical prevention and treatment of Streptococcus pneumoniae infection. Methods:The isolation rate and sample source of Streptococcus pneumoniae isolates as well as age composition of hospitalized children in Bao′an Maternal and Child Health Hospital of Shenzhen city from January 2012 to December 2018 were retrospectively analyzed.The susceptibility of the isolates to antibiotics was tested by disk diffusion method and E-test method. Results:(1) From 2012 to 2018, a total of 90 807 specimens were retrospectively summarized, 9 193 strains of Streptococcus pneumoniae were isolated, with an isolation rate of 10.1%, which was the first pathogen; 98.68% (9 072/9 193 cases) from respiratory tract samples and 97.20% from sputum samples.Among 107 strains isolated from aseptic body fluid specimens, 97 strains were blood specimens. Streptococcus pneumoniae was the most common bacteria with positive culture in aseptic body fluids.(2) The isolation rate of Streptococcus pneumoniae was 10.7% in children under 2 years old, 10.2% in children between 2 and 5 years old and 4.1% in children over 5 years old.About 97% of Streptococcus pneumoniae isolates came from children under 5 years old.(3) According to breakpoints of non-meningitis strains, the sensitivity rate of parenteral Penicillin was 93.18%, the mediation rate was 6.79%, the resistance rate was only 0.03%, the lowest drug concentration to inhibit the growth of 50% bacteria(MIC 50) value was 0.50 and the lowest drug concentration to inhibit the growth of 90% bacteria(MIC 90) value was 2.00; the sensitivity rate of Ceftria-xone was 76.55%, the mediation rate was 20.18%, the resistance rate was 3.26%, the MIC 50 value was 1.00 and the MIC 90 value was 2.00; when interpreted by the breakpoint of meningitis strains, the resistance rate of extra-gastrointestinal Penicillin reached 77.22%, and the mediation rate of Ceftriaxone increased to 30.48% and the drug resistance rate reached 18.45%.The drug resistance rates of Erythromycin, Clindamycin, Tetracycline and Compound neomycin were all over 85.00%.The resistance rates against Levofloxacin and Chloramphenicol were 0.16% and 7.85% respectively.No Vancomycin-resistant Streptococcus pneumoniae was found. Conclusions:Streptococcus pneumoniae is the first bacterial pathogen causing respiratory tract and invasive infection in hospitalized children under 5 years old in this area.Penicillin is still the preferred drug for non-meningitis pneumococcal infection, but the drug resistance rate is high in meningitis patients.

Objective To evaluate the intervention effect of Yi?Han bilingual health education of schistosomiasis control. Methods Baimiao Village in Daqing Town,Xichang City,where Yi Nationality inhabited,was chosen as a pilot to carry out Yi?Han bilingual health education of schistosomiasis control from 2012 to 2015. The villagers and students in the pilot area were in?vestigated by questionnaires before and after the intervention to understand their awareness and correct behavior status on schis?tosomiasis control. Results After the intervention of Yi?Han bilingual health education of schistosomiasis control for 3 years, the awareness rate and the correct rate of behavior on schistosomiasis control of the villagers in the pilot area improved from 45.79%and 51.12%in 2012 to 97.80%and 98.78%in 2015. As for the students,the two rates mentioned above improved from 64.16%and 60.83%in 2012 to 100%and 98.89%in 2015 respectively,and all the differences between the rates before and af?ter the intervention were statistically significant( all P<0.01). Conclusion The intervention of Yi?Han bilingual health educa?tion of schistosomiasis control can obviously improve the knowledge awareness rates and the correct rates of behavior of the resi?dents and students in the gathering area of Yi Nationality.

Objective To investigate the difference in ocular surface microbiota between dry eye patients and healthy subjects,and discuss the role of microbiota in dry eye.Methods Twenty cases of dry eye patients and 90 cases of healthy subjects were collected in the PLA General Hospital and Zhongshan Ophthalmic Center.The samples of conjunctiva impression cytology were collected from all subjects,and then metagenomic shotgun sequencing was performed following the DNA extraction.The differences in alpha diversity and metabolic pathways of the ocular surface microbiota between dry eye patients and healthy subjects were evaluated.Results There was no significant difference in alpha diversity of the microbial community between dry eye patients and healthy subjects (P =0.13).However,an increase of 15 species and a decrease of 10 species were detected on the ocular surface of dry eye patients.The enriched antibiotic resistance genes in dry eye patients were more than healthy subjects.Conclusion Although the alpha diversity of the microbial community on ocular surface between dry eye patients and healthy subjects are not distinguishable,a significant difference could be found in relative abundance and metabolic pathways,suggest that these specific microbiome may be related to the pathogenesis and disease progression of dry eye.

Objective To understand the impact of Qionghai Lake wetland ecological protection construction on the preva?lence of schistosomiasis,so as to provide the evidence for formulating the strategies for schistosomiasis control and prevention. Methods A retrospective survey of the construction of Qionghai Lake wetland was performed,and eleven villages around the wetland were surveyed for schistosomiasis endemic situation. The influence of the wetland project on the schistosomiasis preva?lence and Oncomelania hupensis snail status were investigated. Results Before the construction of Qionghai Lake wetland,the snail elimination and extended chemotherapy for residents was performed. After the project was finished,the roads and ditches were hardened. From 2009 to 2014,the schistosome infection rate of residents declined from 0.37% to 0. No schistosome infect?ed snails were found and in recent 2 years,no snails were found. No mice were infected in the sentinel tests. Conclusions The construction of Qionghai Lake wetland effectively eliminates snails,and interrupts the transmission of schistosomiasis. Howev?er,the environment of the wetland is more suitable for snail breeding,and therefore,the surveillance still should be strength?ened.