ABSTRACT
Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions, etc. Internal causes include age, sex, disease, etc. This paper analyzes and systematically combs how independent variables and covariates directly or indirectly affect the three time-related factors by affecting the body's physiology and internal environment, thus changing the complex process of Fa. Understanding this theoretical framework can better optimize the independent variables to reduce the impact of covariates on Fa. In addition, this paper also introduces the latest progress of prediction and evaluation of Fa, including the progress of complex dissolution device and the status of software prediction.
ABSTRACT
Objective:To investigate the impact of daily step count on glycemic outcomes in community residents with impaired glucose tolerance (IGT).Methods:This was a prospective cohort study, in October 2018, 204 residents who met the criteria of IGT were recruited in the Shijingshan District in Beijing. The subjects were tested for fasting blood glucose, oral glucose tolerance test 2-hour blood glucose (2hBG), glycated hemoglobin A 1c (HbA 1c), lipid profile, liver and kidney function, as well as measurements of height, weight and waist circumference. A dedicated mobile application was used to deliver prediabetes health knowledge monthly. Online guidance was provided to answer questions and daily step count was collected using the application. Three years later, a follow-up was conducted to assess the participants′ glycemic outcomes and other indexes, and a total of 142 participants completed the follow-up review. According to daily step count, the subjects were categorized into high step count group (42 cases,>7 000 steps daily), moderate step count group (54 cases, 5 000-7 000 steps daily), and low step count group (46 cases,<5 000 steps daily). Subjects were categorized into diabetes group (30 cases), prediabetes group (77 cases) and normal glucose tolerance group (35 cases) with glycemic outcomes. Independent sample t test was used to compare the differences in blood glucose, blood lipids, and step counts between the two groups. Kruskal-Wallis H test or one-way ANOVA was used to compare the differences in blood glucose, blood lipids, and step counts between multiple groups. The χ2 test was used to compare the differences in glycemic outcomes between multiple groups. Multivariate logistic regression analysis was used to assess the impact of daily step counts and body mass index on glycemic outcomes. Linear regression analysis was used to evaluate the relationship between daily step counts and 2 h BG. Results:A total of 142 participants completed the 3-year follow-up, including 43 males and 99 females, with a mean age of (60.15±5.67) years. At baseline, males had significantly higher body mass index, waist circumference, and fasting blood glucose when compared to those in females [(26.97±2.43) vs (24.89±2.93) kg/m 2, (92.68±7.75) vs (83.83±8.60) cm, (5.83±0.61) vs (5.62±0.52) mmol/L], the total cholesterol and HDL-C were also significantly lower in males than those in females [(5.10±1.16) vs (5.55±0.95) mmol/L, (1.35±0.34) vs (1.56±0.35) mmol/L] (all P<0.05). After 3-year follow-up, 21.1% (30/142) of IGT participants progressed to diabetes, with an annual conversion rate of approximately 7%. The normal glucose tolerance group showed significantly higher daily step counts when compared with the prediabetes and diabetes groups [(7 886±2 867) vs (5 981±2 655) vs (4 117±2 674) steps] ( H=31.778, P<0.001). Individuals with higher daily step counts exhibited lower body mass index, 2 h BG, and HbA 1c level when compared with those in the ones with moderate and low step counts [(24.26±3.09) vs (25.44±3.38) vs (26.26±3.59) kg/m 2, (7.50±1.71) vs (9.15±3.30) vs (11.19±3.84) mmol/L, 5.97%±0.46% vs 6.14%±0.99% vs 6.40%±0.96%] (all P<0.05). Higher step count was positively correlated with the reversal of prediabetes to normal blood glucose levels (moderate step count, OR=0.297, 95% CI: 0.109-0.804; low step count, OR=0.055, 95% CI: 0.010-0.287), lower daily step count correlated positively with prediabetes progressing to diabetes ( OR=4.857, 95% CI: 1.140-20.689) (all P<0.05). For every additional 1 000 steps per day, the 2 h BG decreased by 0.5 mmol/L. Conclusion:As daily step count increases, the glucose metabolism improves in IGT community residents. Higher daily step count is associated with reversal of IGT to normal glucose tolerance, while lower daily step count may be associated with the progression of IGT to diabetes.
ABSTRACT
Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.
ABSTRACT
Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.
ABSTRACT
ObjectiveTo investigate the potential mechanisms of Jiawei Jingqin Decoction （加味荆芩汤） in the treatment of rosacea. MethodsFifty 8-week-old female BALB/c mice were randomly divided into normal control group， model group， and Jiawei Jingqin Decoction low， medium， and high-dose groups， with 10 mice in each group. Except for the normal control group， mice in the other groups were injected with 40μl of antimicrobial peptide LL-37 at a concentration of 320 μmol/L on the back， repeated once every 12 hours for a total of 4 injections， to induce the rosacea mouse model. The mice in the normal control group were injected with 40 μl of PBS solution at the same time. After successful modeling， the mice in the Jiawei Jingqin Decoction low， medium， and high-dose groups were orally administered Jiawei Jingqin Decoction at doses of 4.35， 8.71， and 17.42 g/（kg·d） respectively， while the mice in the normal control group and the model group were orally administered 20 ml/（kg·d） of normal saline. All groups were treated once daily for 5 days. The changes in skin lesions were observed， and the erythema area was measured and scored. Skin tissue at the injection site was collected for histopathological examination using HE staining， and the number of mast cells was detected using toluidine blue staining. The levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in the skin lesion tissues were measured using the ELISA method. The mRNA expression levels of key factors in the innate immune response pathway of rosacea disease mechanism， including Toll-like receptor 2 （TLR2）， downstream molecules serine protease kallikrein 5 （KLK5） and matrix metalloproteinase 9 （MMP-9）， as well as related inflammatory factors （IL-1β， IL-6， TNF-α）， and adaptive immune CD4+ T cell-related factors interferon-gamma （INF-γ） mRNA were detected using RT-qPCR. Immunohistochemical staining was performed to detect the protein expression of KLK5， MMP-9， and the number of CD4+ T-positive cells. Western blot analysis was used to determine the protein expression levels of CD4+ T cell-related factors including IFN-γ， CC chemokine receptor 5 （CCR5）， signal transducer and activator of transcription 1 （STAT1）， signal transducer and activator of transcription 3 （STAT3）. ResultsThe skin at the injection site on the back of mice in the normal control group appeared normal without any skin lesions or erythema， and histopathological examination showed no infiltration of inflammatory cells. The model group had significantly higher erythema scores and larger erythema areas compared to the normal control group （P＜0.05）， and histopathological examination revealed a significant infiltration of inflammatory cells， with some signs of deep connective tissue damage. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a significant decrease in erythema scores and erythema areas （P＜0.05）， as well as a reduction in inflammatory exudates and inflammatory cell infiltration. However， the Jiawei Jingqin Decoction low-dose group did not show significant difference （P＞0.05）， but there was a slight reduction in inflammatory cell infiltration compared to the model group. When compared to the normal control group， the rosacea skin tissues of the model group showed an increase in the number of mast cells， levels of IL-1β， IL-6， TNF-α， mRNA expression of IL-1β， IL-6， TNF-α， TLR2， INF-γ， KLK5， MMP-9， protein expression of KLK5， MMP-9， and the number of CD4+ T-positive cells （P＜0.05）. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a decrease in the number of mast cells， levels of IL-1β， mRNA expression of IL-1β， TNF-α， and the number of CD4+ T-positive cells. The Jiawei Jingqin Decoction high-dose group showed a decrease in IL-6， TNF-α levels， mRNA expression of IL-6， TLR2， INF-γ， MMP-9， protein expression of MMP-9， KLK5， and the number of CD4+ T-positive cells， as well as a decrease in IFN-γ and STAT1 protein expression （P＜0.05） compared to the Model group. ConclusionJiawei Jingqin Decoction has significant improvement effect on the skin symptoms of roseacne in a mouse model. Its mechanism might be related to regulating skin immune inflammatory reactions， thereby reducing the release of pathogenic factors and inflammatory factors.
ABSTRACT
Anterior cruciate ligament (ACL) rupture leads to weakened quadriceps muscle strength and a decline in proprioception, impairing the neuromuscular control of the lower extremities. ACL reconstruction, aimed at addressing such structural and functional instability, has become a primary treatment method for young and active patients. Consequently, there have been significant advancements in surgical techniques, resulting in improved clinical outcomes. However, achieving successful outcomes after ACL reconstruction is not solely dependent on the surgery itself; pre- and postoperative rehabilitation and management are equally crucial. A well-designed functional recovery program based on medical evidence before and after ACL reconstruction plays a vital role in restoring function to preinjury levels. The process of the functional recovery program, from presurgery to sports return, should adhere to certain principles. These principles involve prompt and accurate clinical diagnosis and patient classification after injury, systematic programs addressing joint swelling and inflammation control, reduction of arthrogenic muscle inhibition, restoration of range of motion, muscle strength recovery, and proprioception restoration. Postoperatively, it is essential to go beyond traditional methods (such as range of motion restoration and muscle strengthening) by implementing a functional recovery program that includes enhancement of proprioception and neuromuscular control system from the early stages, considering the biological healing response of the graft. This comprehensive approach is vital for achieving optimal outcomes in the recovery of function after ACL reconstruction.
ABSTRACT
Objective:To investigate the iodine nutritional status of children and the consumption condition of non-iodized salt in Henan Province after implementation of the new standard of "Definition and demarcation of water-borne iodine-excess areas and iodine-excess endemial areas" (GB/T 19380-2016, hereinafter referred to as new standard) for four years (2021), and to provide a basis for scientific adjustment of intervention strategies.Methods:In 2021, according to the requirements of the new standard and based on the results of the water iodine survey in Henan Province from 2017 to 2020, a survey was conducted on the iodine nutrition status of children in water-borne high iodine areas in 47 counties (cities, districts, hereinafter referred to as counties) with high iodine administrative village (neighborhood committee, hereinafter referred to as administrative village). In each county, 5 administrative villages with median water iodine > 100 μg/L were selected as the investigation villages, and water samples were collected to determine the water iodine value. Forty non-boarding students aged 8 - 10 (age balanced, half male and half female, age increased to 6 - 12 when less than 40) were selected from each village as investigation subjects. Salt samples from their homes and urine samples were collected to detect salt iodine and urine iodine content, and thyroid volume of children was measured. And the monitoring results of areas where the supply of iodized salt had been suspended for less than 4 years (in newly high iodine areas) and more than 10 years (in previously high iodine areas) were further compared and analyzed.Results:A total of 257 administrative villages in the province were monitored, and the range of water iodine was 1.6 - 609.5 μg/L, with a median of 132.5 μg/L. A total of 8 611 children were tested for salt iodine, urine iodine and thyroid volume. The non-iodized salt rate was 58.3% (5 017/8 611), and the median urine iodine was 342.2 μg/L, thyroid enlargement rate was 2.9% (250/8 611). The median water iodine (153.0 vs 118.4 μg/L), the median urine iodine in children (371.6 vs 287.7 μg/L) and the goiter rate [3.8% (211/5 537) vs 1.3% (39/3 074)] in the newly high iodine areas were higher than those in the previously high iodine areas, and the differences were statistically significant ( Z = 583.12, - 14.09, P < 0.001; χ 2 = 44.40, P < 0.001); the non-iodized salt rate was lower than that of the previously high iodine areas [37.2% (2 057/5 537) vs 96.3% (2 960/3 074)], and the difference was statistically significant (χ 2 = 2 841.37, P < 0.001). Conclusions:The iodine nutrition level of children in water-borne high iodine areas of Henan Province in 2021 is at an excess level, but the non-iodized salt rate in residential households is low. We should make every effort to ensure the precise supply of non-iodized salt in high iodine areas after implementation of the new standard, and strengthen iodine nutrition monitoring and health education for key populations to prevent the occurrence of high iodine hazards.
ABSTRACT
Objective:To investigate the iodine nutrition level and thyroid function status of pregnant women in Hubei Province.Methods:According to the requirements of "the National Iodine Deficiency Disorders Monitoring Program (2016 Edition)", in 2020, using a cross-sectional survey method, two mountainous counties and two plain areas in Hubei Province were divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) as survey subjects. Urine iodine content and thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] were tested. Abnormal thyroid function rate and antibody positive rate were analyzed, and correlation analysis of thyroid function indicators was conducted (Spearman method). Results:A total of 321 pregnant women were included, including 43, 114, and 164 in early, middle, and late pregnancy, respectively; The median urinary iodine was 164.80 μg/L. The median serum FT 3, FT 4, TSH, TPOAb, TgAb levels were 4.10, 12.83 pmol/L, 1.85 mU/L, 15.84 and 13.35 U/ml, respectively. There were statistically significant differences in FT 3, FT 4, and TSH levels among different trimesters ( P < 0.05). According to Spearman's correlation analysis, FT 3 in early stage of pregnancy was negatively correlated with TSH and TPOAb levels ( r = - 0.46, - 0.33, P < 0.05), while TSH was positively correlated with TPOAb level ( r = 0.33, P = 0.032); there was a positive correlation between FT 4 and TgAb levels in middle stage of pregnancy ( r = 0.21, P = 0.032); there was a negative correlation between FT 3 and TPOAb levels in late stage of pregnancy ( r = - 0.19, P = 0.017); FT 3 and FT 4, TPOAb and TgAb levels were positively correlated throughout pregnancy ( P < 0.05). There was no correlation between urinary iodine content and thyroid function indicators ( P > 0.05). The total abnormal rate of thyroid function was 7.79% (25/321), with 16.28% (7/43), 5.26% (6/114), and 7.32% (12/164) in early, middle, and late pregnancy, respectively. There was no statistically significant difference in the abnormal rate of thyroid function among different pregnancy periods (χ 2 = 4.83, P = 0.097). The detection rates of hypothyroxinemia, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism were 4.36% (14/321), 0.31% (1/321), 2.49% (8/321), 0.31% (1/321), and 0.31% (1/321), respectively. The positive detection rate of autospecific antibodies was 10.28% (33/321), with a TPOAb positive detection rate of 9.97% (32/321) and a TgAb positive detection rate of 5.30% (17/321). Conclusions:The iodine nutrition level of pregnant women in Hubei Province is at a suitable level, and the rates of abnormal thyroid function and thyroid autospecific antibody positive are relatively low. It is necessary to continuously monitor the iodine nutrition and thyroid function indexes of pregnant women, strengthen health education on the hazards of iodine deficiency during pregnancy, and minimize the harm to maternal and infant health caused by iodine deficiency.
ABSTRACT
Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
ABSTRACT
Background Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis. Methods The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis. Results We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes. Conclusion Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.
ABSTRACT
ObjectiveTo analyze the prevalence of HCV antibody positive and associated factors among drug users in Dehong Prefecture， Yunnan， and to provide scientific evidence for HCV prevention. MethodsQuestionnaire surveys and serological testing were conducted among 400 drug users continuously selected from four national AIDS sentinel surveillance in Dehong Prefecture between January and July during 2014‒2021. Results11 683 drug users were included. The prevalence of HCV antibody positive was 20.2% overall， and 14.9%， 20.1%， 22.4%， 19.8%， 22.5%， 20.6%， 24.5%， 19.0% from 2014 to 2021， respectively （trend Z=-3.78， P<0.001）. Multivariable analysis indicated the following were independently associated with HCV antibody positive： that older age （OR=1.02， 95%CI： 1.02‒1.03）， male （OR=1.70， 95%CI： 1.19‒2.42）， unmarried （OR=1.64， 95%CI： 1.44‒1.87）， divorced or widowed （OR=1.73， 95%CI： 1.48‒2.02）， Jingpo ethnicity （OR=1.39， 95%CI： 1.19‒1.63）， injection drug use （OR=15.46， 95%CI： 13.13‒18.12）， and HIV infection（OR=4.96， 95%CI：4.12‒5.99）. ConclusionThe prevalence of HCV antibody positive among drug users in Dehong Prefecture is high and increases with some fluctuations during 2014 to 2021， which highlights the need to develop interventions targeting this population.
ABSTRACT
Objective@#: The use of indocyanine green videoangiography (ICG-VA) to assess blood flow in the brain during cerebrovascular surgery has been increasing. Clinical studies on ICG-VA have predominantly focused on qualitative analysis. However, quantitative analysis numerical modelling for time profiling enables a more accurate evaluation of blood flow kinetics. In this study, we established a multiple exponential modified Gaussian (multi-EMG) model for quantitative ICG-VA to understand accurately the status of cerebral hemodynamics. @*Methods@#: We obtained clinical data of cerebral blood flow acquired the quantitative analysis ICG-VA during cerebrovascular surgery. Varied asymmetric peak functions were compared to find the most matching function form with clinical data by using a nonlinear regression algorithm. To verify the result of the nonlinear regression, the mode function was applied to various types of data. @*Results@#: The proposed multi-EMG model is well fitted to the clinical data. Because the primary parameters—growth and decay rates, and peak centres and heights—of the model are characteristics of model function, they provide accurate reference values for assessing cerebral hemodynamics in various conditions. In addition, the primary parameters can be estimated on the curves with partially missed data. The accuracy of the model estimation was verified by a repeated curve fitting method using manipulation of missing data. @*Conclusion@#: The multi-EMG model can possibly serve as a universal model for cerebral hemodynamics in a comparison with other asymmetric peak functions. According to the results, the model can be helpful for clinical research assessment of cerebrovascular hemodynamics in a clinical setting.
ABSTRACT
Background@#Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease. @*Objectives@#We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats. @*Methods@#Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed. @*Results@#After exposure to CA and NaOCl, body weight loss was observed but recovered.Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females. @*Conclusions@#The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.
ABSTRACT
Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.
ABSTRACT
As nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 is immunogenic but not targeted in vaccines, it could be useful in distinguishing natural infection from vaccination. We aimed to investigate the clinical utility of sero-immunological responses against the nucleocapsid protein. Nucleocapsid antibody immunoassay study with 302 coronavirus disease 2019 (COVID-19) patients showed lower titers in immunocompromised patients (P < 0.001), higher titers in higher severity (P = 0.031), and different seroconversion rates and titers according to variants of concern. Longitudinal evaluation of nucleocapsid antibodies using 513 samples from 291 COVID-19 patients revealed that it could persist up to 556 days from symptom onset. Interferon gamma release assay against the nucleocapsid protein showed poor response, precluding the deduction of a cut-off for the nucleocapsid protein. In conclusion, nucleocapsid antibody provides instructive clues about the immunogenicity of nucleocapsid proteins by different seroconversion rates and titers according to the severity of infection, host immune status, and different variants of concern.
ABSTRACT
Purpose@#Ketogenic diets (KDs) have anti-obesity effects that may be related to glucose control and the gut microbiota. This paper hypothesizes that KD reduces body weight and changes the insulin sensitivity and gut microbiota composition in a mouse model of dietinduced obesity. @*Methods@#In this study, C57BL/6 male mice were assigned randomly to 3 groups. The assigned diets were provided to the control and high-fat (HF) diet groups for 14 weeks. The KD group was given a HF diet for 8 weeks to induce obesity, followed by feeding the KD for the next 6 weeks. @*Results@#After the treatment period, the KD group exhibited a 35.82% decrease in body weight gain compared to the HF group. In addition, the KD group demonstrated enhanced glucose control, as shown by the lower levels of serum fasting glucose, serum fasting insulin, and the homeostatic model assessment of insulin resistance, compared to the HF group. An analysis of the gut microbiota using 16S ribosomal RNA sequencing revealed a significant decrease in the proportion of Firmicutes when the KD was administered. In addition, feeding the KD reduced the overall alpha-diversity measures and caused a notable separation of microbial composition compared to the HF diet group. The KD also led to a decrease in the relative abundance of specific species, such as Acetatifactor_muris, Ligilactobacillus_apodemi, and Muribaculum_intestinale, compared with the HF group. These species were positively correlated with the body weight, whereas the abundant species in the KD group (Kineothrix_alysoides and Saccharofermentans_acetigenes) showed a negative correlation with body weight. @*Conclusion@#The current study presents supporting evidence that KD reduced the body weight and altered the insulin sensitivity and gut microbiota composition in a mouse model of diet-induced obesity.
ABSTRACT
Objectives@#The coronavirus disease 2019 (COVID-19) pandemic has led to a decrease in face-to-face classes worldwide, affecting the mental health of children and their parents. The global pandemic has increased children’s overall use of electronic media. This study analyzed the effect of children’s screen time on problematic behaviors during the COVID-19 pandemic. @*Methods@#A total of 186 parents from Suwon, South Korea, were recruited to participate in an online survey. The mean age of the children was 10.14 years old, and 44.1% were females. The questionnaire included questions on children’s screen time, problematic behaviors, and parental stress. Children’s behavioral problems were evaluated using the Behavior Problem Index, whereas the Parental Stress Scale was used to estimate parental stress. @*Results@#The mean smartphone usage frequency of the children was 5.35 days per week, and the mean smartphone screen time was 3.52 hours per day. Smartphone screen time (Z=4.49, p<0.001) and usage frequency (Z=2.75, p=0.006) were significantly correlated with children’s behavioral problem scores. The indirect effect of parental stress on this relationship was also statistically significant (p=0.049, p=0.045, respectively). @*Conclusion@#This study suggests that children’s smartphone screen time has affected problematic behaviors during the COVID-19 pandemic. Furthermore, parental stress is related to the relationship between children’s screen time and problematic behaviors.
ABSTRACT
This study aimed to determine foodservice and hygiene management statuses at welfare facilities catering to disabled persons by facility type to provide basic data for foodservice management guidelines. An online survey was distributed to workers at 1,984 welfare facilities for disabled persons in Korea, and 531 facilities responded, which represented a response rate of 26.8%. The survey requested general information about the facilities, facility users, meals, hygiene, and management. Statistical analyses were performed, and frequency analysis and the chi-square test were used to investigate responses by facility type. The survey results revealed that daycare centers were most common and accounted for 27.4% of responses. Residential facilities for the severely disabled and sheltered workshops accounted for 16.9% and 16.4%, respectively, and residential facilities by disability type accounted for 13.0%. The presence of dietitians at welfare facilities varied by facility type. Welfare centers for the disabled (94.7%) had the highest percentage of dietitians, followed by residential facilities for the severely disabled (87.8%). On the other hand, sheltered workshops and daycare centers for disabled persons had the lowest percentages of dietitians (10.3% and 4.1%, respectively). This study highlights the variations that exist in foodservice management across different welfare facilities for disabled persons and emphasizes the challenges faced by those responsible for managing foodservices and maintaining hygiene, particularly in large facilities with no dietitians. Therefore, we recommend tailored meal management guidelines be developed for each type of welfare facility for disabled persons.
ABSTRACT
Purpose@#We investigated the ophthalmic manifestations observed in patients diagnosed with ocular myasthenia gravis. @*Methods@#In total, 58 patients diagnosed with ocular myasthenia gravis visited the ophthalmology and neurology departments between January 2011 and August 2022. Patients were followed for > 6 months; their ophthalmic manifestations were analyzed retrospectively. @*Results@#The study included 29 males and 29 females with a mean age of 55.52 ± 15.60 years. Among the patients, 31 tested positive for anti-acetylcholine receptor antibodies, resulting in a positive rate of 53.45%. Abnormalities in repeated nerve stimulation tests were observed in 33.33% of the patients. The antibody-positive group exhibited a higher frequency of progression to generalized myasthenia gravis (p = 0.011) and a higher incidence of chest abnormalities (p < 0.001) compared to the antibody-negative group. Horizontal and vertical diplopia were commonly observed in a complex group of patients with diplopia and blepharoptosis (p < 0.001); there was a difference in the pattern of strabismus between the diplopia single group with esotropia and the complex group with exotropia (p = 0.029). In addition, the combination group demonstrated a higher antibody titer (p = 0.034), a higher frequency of abnormalities in repeated nerve stimulation tests (p = 0.022), and a higher incidence of chest abnormalities (p = 0.022). @*Conclusions@#The anti-acetylcholine receptor antibody-positive group had a higher incidence of progression to generalized myasthenia gravis; moreover, the complex group of patients with diplopia and ptosis exhibited elevated levels of anti-acetylcholine receptor antibodies and frequently accompanied both horizontal and vertical strabismus.
ABSTRACT
ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.