OBJECTIVE To analyze the influencing factors for achieving target plasma drug concentration （trough） （abbreviated as “PDC”） of vancomycin in patients from high-altitude regions and establish a predictive model for PDC using single- center data， providing references for rational clinical drug use. METHODS Inpatients with vancomycin （1 g， q12 h） administered intravenously in our hospital from January 2021 to June 2024 were retrospectively included. Demographic data， liver and kidney function and hematological indexes were collected. Spearman correlation analysis was used to evaluate the correlation between vancomycin PDC and each detection index. Univariate analysis was used to evaluate the differences of each index in patients with different PDC， and the effects of different gender， body mass index， age and underlying diseases （hypertension/diabetes） on vancomycin PDC. Based on the results of correlation analysis and univariate analysis， multiple linear stepwise regression analysis was used to obtain the independent predictors of vancomycin PDC and construct the prediction model. RESULTS A total of 141 patients were included， with an overall attainment rate of 46.81% for the target PDC of vancomycin. Correlation analysis showed that the vancomycin PDC was positively correlated with age， blood urea nitrogen， uric acid （UA）， serum creatinine （CRE） and β2- microglobulin （β2-MG）， and negatively correlated with height， weight， creatinine clearance rate （CCR）， glomerular filtration rate （GFR）， alanine transaminase （ALT）， hemoglobin （HGB）， white blood cell count and neutrophils （P＜0.05）. There were significant differences in age， CRE and other 14 indexes among different PDC groups （P＜0.05 or P＜0.01）. Age and underlying diseases had significant effects on vancomycin PDC （P＜0.05 or P＜0.01）. CCR， direct bilirubin （DBil）， β2-MG， UA， HGB and height （standardized coefficients were －0.371， 0.367， 0.169， 0.232， －0.140， －0.132； P＜0.05） were independent predictors of vancomycin PDC. The F value of the regression equation was 34.858 （P＜0.05）， the R2 was 0.610， and the adjusted R2 was 0.592. CONCLUSIONS The vancomycin PDC of patients in high-altitude regions is affected by multiple factors such as renal function， liver function and hematological indexes. CCR， HGB and height could be used to predict vancomycin PDC negatively， while DBil， β2-MG and UA could be used to predict vancomycin PDC positively. The variables of the established prediction model could explain 59.2% of the variation of vancomycin PDC.

ObjectiveTo investigate the predictive factors for HBsAg clearance in chronic hepatitis B （CHB） patients with a low level of hepatitis B surface antigen （HBsAg） treated with pegylated interferon α-2b （PEG-IFN-α-2b）， to establish a combined predictive model and a nomogram based on multiple factors， and to provide a reference for formulating individualized treatment regimens and predicting treatment outcome in clinical practice. MethodsA retrospective analysis was performed for 167 CHB patients with HBsAg <1 500 IU/mL who attended The Third People’s Hospital of Kunming from January 2022 to January 2024 and were treated with PEG-IFN-α-2b. According to whether clinical cure was achieved， the patients were divided into HBsAg clearance group and HBsAg non-clearance group. Related data were collected， including general information and serological/biochemical/virological indicators at different time points during treatment. The independent samples t-test was used for comparison of normally distributed continuous data， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data； the chi-square test was used for comparison of categorical data. The multivariate logistic regression analysis was used to identify independent influencing factors. The receiver operating characteristic （ROC） curve was used to assess the value of indicators used alone or in combination in predicting clinical cure， and calibration curves were plotted to assess the risk prediction model. ResultsThe univariate analysis showed that there were significant differences between the two groups in age （t=-6.839， P<0.05）， history of nucleos（t）ide analogue treatment for over 1 year （χ²=59.339， P<0.05）， genotype （χ²=4.610， P<0.05）， nonalcoholic fatty liver disease （χ²=5.319， P<0.05）， hepatitis B virus DNA status before treatment （χ²=60.861， P <0.05）， compensated liver cirrhosis （χ²=10.960， P<0.05）， HBeAg status before treatment （χ²=19.060， P<0.05）， a history of interferon treatment （χ²=8.162， P<0.05）， presence of interferon antibodies after treatment （χ²=12.858， P<0.05）， HBsAg level before treatment （Z=-7.412， P<0.05）， alanine aminotransaminase （ALT） level at baseline （Z=-6.117， P<0.05）， ALT level at 12 weeks of treatment （Z=-7.171， P<0.05）， platelet count （PLT） at 24 weeks of treatment （Z=-3.622， P<0.05）， and thyroid stimulating hormone （TSH） level at 24 weeks of treatment （Z=-2.830， P<0.05）. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.230， P=0.007）， history of nucleos（t）ide analogue treatment for over 1 year （OR=0.008， P=0.011）， HBeAg status before treatment （OR=0.003， P=0.012）， HBsAg level before treatment （OR=1.005， P=0.014）， ALT level at baseline （OR=0.949， P=0.014）， ALT level at 12 weeks of treatment （OR=0.969， P=0.016）， PLT at 24 weeks of treatment （OR=0.969， P=0.022）， and TSH level at 24 weeks of treatment （OR=3.608， P=0.045） were independent influencing factors for HBsAg clearance at 48 weeks of treatment in CHB patients with HBsAg <1 500 IU/mL. The Hosmer-Lemeshow goodness-of-fit test yielded χ²=1.398， P=0.994， indicating that the model had good fitting. The Bootstrap method was used to perform internal validation of the nomogram model， and there was a good degree of fitting between the calibration curve and the ideal curve， with a mean absolute error of 0.029. The ROC curve analysis showed that the combination of predictive factors had an area under the ROC curve of 0.982 （95% confidence interval： 0.961 — 0.999）， with a sensitivity of 94.10% and a specificity of 93.10%， suggesting that the nomogram model had a good discriminatory ability. For the CHB patients with HBsAg <1 500 IU/mL and different features， further analysis of HBsAg clearance rate at 48 weeks of treatment showed an HBsAg clearance rate of 69.60% for those with HBsAg ≤67.65 IU/mL before treatment， 58.30% for those with a baseline ALT level of ≥62.50 U/L， 68.30% for those with an ALT level of ≥92.50 U/L at 12 weeks of treatment， 42.40% for those with PLT ≥104×10⁹/L at 24 weeks of treatment， and 48.30% for those with a TSH level of ≤1.38 μIU/mL at 24 weeks of treatment， with significant differences between the two groups （all P<0.001）. ConclusionAge， history of nucleos（t）ide analogue treatment for over 1 year， HBeAg status before treatment， HBsAg level before treatment， baseline ALT level， ALT level at 12 weeks of treatment， PLT level at 24 weeks， and TSH level at 24 weeks of treatment are independent predictive factors. The combined prediction nomogram model constructed in this study has a relatively high value in predicting clinical cure at 48 weeks of PEG-IFN-α-2b treatment in CHB patients with HBsAg<1 500 IU/mL， thereby providing a reference for selecting suitable treatment population and predicting clinical cure.

ObjectiveTo construct and validate a predictive model for hepatic encephalopathy （HE） in patients with end-stage liver disease （ESLD） by combining key indicators such as cytokines and Model for End-Stage Liver Disease （MELD） score， and to provide evidence-based support for the early identification of high-risk populations and the optimization of intervention strategies in clinical practice. MethodsA retrospective analysis was performed for 2 167 patients with ESLD who were admitted to The Third People’s Hospital of Kunming from January 2022 to December 2024， the patients were divided into a training set with 1 517 patients and a validation set with 650 patients at a ratio of 7∶3 using the stratified random sampling method. A univariate analysis and a least absolute shrinkage and selection operator （LASSO） regression analysis were performed for the training set to identify potential influencing variables， and then a binary Logistic regression model was constructed to investigate the independent influencing factors for HE in ESLD patients. A nomogram prediction model was established based on this regression model， and the Hosmer-Lemeshow goodness-of-fit test was performed. The receiver operating characteristic （ROC） curve， calibration curves， decision curve analysis， and clinical impact curve were used to comprehensively evaluate the degree of fit， accuracy， consistency， and clinical practicability of the predictive model derived from the training set. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. ResultsThe univariate analysis showed that there were significant differences between the study group and the control group in age， sex， blood ammonia， lymphocytes， hemoglobin， platelet count， prothrombin time， fibrinogen， international normalized ratio， total bilirubin， aspartate aminotransferase， total protein， albumin， prealbumin， alkaline phosphatase， cholinesterase， total bile acid， triglyceride， total cholesterol， high-density lipoprotein， low-density lipoprotein， blood glucose， CD3⁺ T cells， CD4⁺ T cells， CD8⁺ T cells， high-sensitivity C-reactive protein， carcinoembryonic antigen， triiodothyronine， thyroxine， free triiodothyronine， free thyroxine， interleukin-1β， interleukin-5， interleukin-6， interleukin-8， interleukin-12p70， interleukin-17， interferon-γ， and MELD score （all P<0.05）. The LASSO regression analysis identified nine variables of age， blood ammonia， albumin， prealbumin， cholinesterase， total cholesterol， thyroxine， interleukin-17， and MELD score， and the binary Logistic regression analysis showed that blood ammonia， interleukin-17， and MELD score were independent risk factors for HE in ESLD patients， while age and thyroxine were independent protective factors （all P<0.05）. A nomogram model was constructed based on these five variables. The Hosmer-Lemeshow goodness-of-fit test in the training set showed a good degree of fit （P=0.207）， with a McFadden’s pseudo-R² of 0.184， suggesting that the model had acceptable explanatory power； the Hosmer-Lemeshow goodness-of-fit test in the internal validation set further confirmed the calibration stability of the model （P=0.067）， suggesting that the model had a good degree of fit in independent data. The model had an area under the ROC curve of 0.784 in the validation set， with a sensitivity of 0.710 and a specificity of 0.752. The mean absolute error of the calibration curve was 0.067， and decision curve analysis and clinical impact curve showed that the nomogram model had positive net benefit and good clinical practicability. ConclusionThe nomogram model constructed based on age， blood ammonia， thyroxine， interleukin-17， and MELD score for predicting HE in patients with ESLD has a good degree of fit， high accuracy and consistency， and excellent clinical practicability.

Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

Radiation prevention and treatment drugs are a rapidly developing field.Radiation prevention and treatment drugs can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds,which are widely used in medical,scientific research and other fields.This paper reviews the classification of radiation prevention and treatment drugs,which can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds.At the same time,its mechanism of action and clinical application are elaborated in detail,and the risk assessment is carried out from the aspects of effectiveness,safety and drug interaction.Finally,the risk reduction strategies are summarized from the aspects of clinical medication specification and monitoring,continuous drug safety research,improvement of emergency reserve and support capacity and construction of full-cycle regulatory system,so as to provide reference for the rational application and further research of radiation prevention and treatment drugs.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To investigate the association of serum levels of myoglobin(Myo)and reticulocyte(Ret)with cardiac function class in patients with chronic heart failure(CHF).Methods:A total of 106 CHF patients treated in First Rongjun Special Care Hospital of Hebei Province between February 2020 and February 2024 were retrospec-tively selected as the observation group.According to New York Heart Association(NYHA)cardiac function class,patients were divided into class Ⅱ group(n=61)and class Ⅲ～Ⅳ group(n=45),and 107 healthy people with nor-mal physical examination results were selected from our hospital simultaneously as control group.The Myo and Ret levels were compared between control group and observation group,class Ⅱ group and class Ⅲ～Ⅳ group.Spearman correlation analysis was used to analyze the association of Myo and Ret levels with NYHA class in CHF patients.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of Myo,Ret and their combined detection for NYHA class Ⅲ～Ⅳ in CHF patients.Results:Compared to participants in the control group,those in the observation group had significant higher Myo level[(50.42±9.98)μg/ml vs.(35.22±5.36)μg/ml]and significant lower Ret level[(2.24±0.68)％vs.(2.91±0.61)％](P＜0.001 all).Compared to those in class Ⅱ group,those in class Ⅲ～Ⅳ group had significant higher Myo level[(60.77±5.94)μg/ml vs.(42.79±2.97)μg/ml]and significant lower Ret level[(1.73±0.31)％vs.(2.62±0.62)％](P＜0.001 all).Spearman correlation analysis showed that Myo(r=0.654)was positively correlated with NYHA cardiac function class in CHF patients,while Ret(r=-0.589)was inversely correlated with it(P＜0.001 all).ROC analysis showed that a combination of Myo and Ret had significant higher predictive efficacy(AUC=0.926,95％CI 0.858～0.968)for NYH A class Ⅲ～Ⅳ in CHF patients than Myo(AUC=0.804,95％CI 0.716～0.875)and Ret(AUC=0.701,95％CI 0.604～0.786)alone(Z=2.745,4.183,P＜0.01 both).Conclusion:Our study showed that Myo and Ret levels were significantly correlated with NYHA class in CHF patients.Moreover,a combination of Myo and Ret levels showed better diagnostic value for NYHA class Ⅲ～Ⅳ in this population.

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.