OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Hard capsules of traditional Chinese medicine(TCM) have different degrees of hygroscopicity, which affects the stability and efficacy of drugs. In this paper, 30 kinds of commercially available TCM capsules were used as the research object. The hygroscopicity curves of capsule contents, capsule shells, and capsules were tested respectively, and the first-order kinetic equation was used for fitting. The results show that during the 24 h hygroscopicity process, the capsule shell can reduce the weight gain caused by the hygroscopicity of the contents by 0.80%-53.0% and the hygroscopicity rate of the capsule contents by 1.74%-91.3%, indicating that the capsule shell has a strong delay effect on the hygroscopicity of the contents of the TCM capsules. Seven physical parameters of the contents of 30 kinds of TCM capsules were determined, and 14 prescription process-related parameters were sorted out. A partial least squares model for predicting the hygroscopicity rate of the contents of TCM capsules(with shell) for 24 h was established. It is found that the hygroscopicity rate of the capsule shell is positively correlated with the hygroscopicity of the contents of TCM capsules(with shell), suggesting that the capsule shell with a low hygroscopicity rate is helpful for moisture prevention. In addition, the pre-treatment process route of the preparation and the type of molding raw materials affect the hygroscopicity. A larger proportion of the extract in the capsule content and a smaller proportion of the fine powder of the decoction pieces indicate stronger hygroscopicity of the capsule content. The 24 h hygroscopicity rate of 15% was used as the classification node of hygroscopicity strength, and the hygroscopicity rate constant of 0.58 was used as the classification node of hygroscopicity speed. The classification system of hygroscopicity behaviors of TCM capsules was established: the varieties with strong and fast hygroscopicity accounted for about 6.67%, while those with strong and slow hygroscopicity accounted for about 33.3%; the varieties with weak and fast hygroscopicity accounted for about 26.7%, while those with weak and slow hygroscopicity accounted for about 33.3%. The classification system is helpful to quantify and compare the hygroscopicity behavior of different TCM capsules and provides a reference for the quality improvement, moisture prevention technologies, and material research of TCM capsules.
Medicine, Chinese Traditional ; Wettability ; Capsules ; Powders ; Technology ; Drugs, Chinese Herbal

OBJECTIVES: To evaluate the ability of the ForenSeq^TM DNA Signature Prep kit (ForenSeq kit) in analyzing the sequence information of STRs in Zhejiang She ethnic group and its forensic application efficacy. METHODS: A total of 50 Zhejiang She ethnic group samples were sequenced with the ForenSeq kit on the MiSeq FGx platform. The data was analyzed using ForenSeq^TM universal analysis software to obtain the motif structure and flank regions of the 58 STRs, then compared with PCR-CE typing results to test the consistency. At last, the allele frequency and population genetic parameters were calculated. RESULTS: A total of 448 sequence polymorphic alleles were detected in 50 samples of Zhejiang She ethnic group. Compared with fragment length polymorphism detected by PCR-CE, 82 alleles were increased by MPS detection based on ForenSeq kit, and 7 SNPs variation were detected in the flanking regions of 6 loci. The 22 male individuals were genotyped, and total 19 haplotypes were detected in 24 Y chromosome STRs of these 22 males. The cumulative discrimination power of the 27 autosomal STRs was 1-8.87×10^-30, the cumulative probability of exclusion of duo-testing was 0.999 999 962 640 657, the cumulative probability of exclusion of trios-testing was 0.999 999 999 999 633. CONCLUSIONS Based on MPS typing technology, using the ForenSeq kit greatly improves the detection efficiency. In addition, the 58 STRs have good genetic polymorphisms in Zhejiang She ethnic group, which are suitable for individual identification and paternity identification in forensic application.
DNA ; DNA Fingerprinting/methods* ; Ethnicity/genetics* ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Microsatellite Repeats ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/methods*

Objective: High PM concentration is the main feature of increasing haze in developing states, but information on its microbial composition remains very limited. This study aimed to determine the composition of microbiota in PM in Guangzhou, a city located in the tropics in China. Methods: In Guangzhou, from March 5 to 10 , 2016, PM was collected in middle volume air samplers for 23 h daily. The 16S rDNA V4 region of the PM sample extracted DNA was investigated using high-throughput sequence. Results: Among the Guangzhou samples, , , , , and were the dominant microbiota accounting for more than 90% of the total microbiota, and was the dominant gram-negative bacteria, accounting for 21.30%-23.57%. We examined the difference in bacterial distribution of PM between Beijing and Guangzhou at the genus level; was found in both studies, but was only detected in Guangzhou. Conclusion In conclusion, the diversity and specificity of microbial components in Guangzhou PM were studied, which may provide a basis for future pathogenicity research in the tropics.
Air Microbiology ; Air Pollutants ; analysis ; Bacteria ; classification ; isolation & purification ; China ; Cities ; Environmental Monitoring ; Microbiota ; Particle Size ; Particulate Matter ; analysis ; RNA, Bacterial ; analysis ; RNA, Ribosomal, 16S ; analysis

Objective: Apios americana, a plant used as a staple ingredient of native American diets, has various properties, including anti-cancer, anti-hyperglycemic, hypotensive, and anti-inflammatory activity. In Japan, Apios is used as a post-natal medication. After parturition, women undergo a period of recovery as they return to pre-pregnancy conditions. However, few health products that aid post-partum recovery are on the market. We explored whether Apios can accelerate the post-partum recovery process, in particular the involution of the uterus. Methods: Female rats kept in individual cages were mated with two male rats, with the exception of the control group (female rats without mating, on basal diet; n=6). After delivery, rats were divided into five groups based on their diet: basal diet (model; n=6); basal diet+oral intake at 5.4 g/kg of Chanfukang granules (a Chinese patent medicine preparation for post-partum lochia) (positive; n=6); basal diet containing 10% Apios powder (low; n=6); basal diet containing 20% Apios powder (medium; n=6); basal diet containing 40% Apios powder (high; n=6). Five days later, uteri and spleens were weighed. Uterus and spleen indices for each rat were calculated by dividing visceral weight by the total weight. Hormone and cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Histological analysis of uteri was completed using hematoxylin and eosin (H&E) staining. Expression of matrix metalloproteinases and inhibitors in uteri was measured by western blotting. Results: Our results showed that Apios treatment reduced the post-partum uterus index and regulated the hormone concentrations. Moreover, we found that the process of uterine involution was accelerated, based on morphological changes in the uterus. In addition, our results indicated that Apios alleviated the inflammatory response induced by the involution process. Transforming growth factor ß was also found to be regulated by Apios. There were significant downregulation of matrix metalloproteinases and upregulation of their inhibitors by Apios, which suggested that Apios increased the rate of the collagen clearance process. Conclusions: These results, based on experimental observations at the molecular and protein levels, verified our hypothesis that Apios can improve uterine involution, and demonstrated the potential application of Apios in post-partum care.

OBJECTIVE: Apios americana, a plant used as a staple ingredient of native American diets, has various properties, including anti-cancer, anti-hyperglycemic, hypotensive, and anti-inflammatory activity. In Japan, Apios is used as a post-natal medication. After parturition, women undergo a period of recovery as they return to pre-pregnancy conditions. However, few health products that aid post-partum recovery are on the market. We explored whether Apios can accelerate the post-partum recovery process, in particular the involution of the uterus. METHODS: Female rats kept in individual cages were mated with two male rats, with the exception of the control group (female rats without mating, on basal diet; n=6). After delivery, rats were divided into five groups based on their diet: basal diet (model; n=6); basal diet+oral intake at 5.4 g/kg of Chanfukang granules (a Chinese patent medicine preparation for post-partum lochia) (positive; n=6); basal diet containing 10% Apios powder (low; n=6); basal diet containing 20% Apios powder (medium; n=6); basal diet containing 40% Apios powder (high; n=6). Five days later, uteri and spleens were weighed. Uterus and spleen indices for each rat were calculated by dividing visceral weight by the total weight. Hormone and cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Histological analysis of uteri was completed using hematoxylin and eosin (H&E) staining. Expression of matrix metalloproteinases and inhibitors in uteri was measured by western blotting. RESULTS: Our results showed that Apios treatment reduced the post-partum uterus index and regulated the hormone concentrations. Moreover, we found that the process of uterine involution was accelerated, based on morphological changes in the uterus. In addition, our results indicated that Apios alleviated the inflammatory response induced by the involution process. Transforming growth factor β was also found to be regulated by Apios. There were significant downregulation of matrix metalloproteinases and upregulation of their inhibitors by Apios, which suggested that Apios increased the rate of the collagen clearance process. CONCLUSIONS These results, based on experimental observations at the molecular and protein levels, verified our hypothesis that Apios can improve uterine involution, and demonstrated the potential application of Apios in post-partum care.

OBJECTIVE: To prepare and characterize citric acid (CA)-modified super paramagnetic iron oxide nanoparticles (SPIONs) for magnetic targeting, hyperthermia and magnetic resonance imaging (MRI). METHODS: CA-modified SPIONs (CA-SPIONs) were prepared by co-precipitation method and then the magnetic responsiveness, morphology, particle size, infrared feature, weight percentage of CA, magnetic property and X-ray diffraction pattern of CA-SPIONs were respectively characterized by magnet, transmission electron microscope, laser particle size analyzer, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry-differential thermal analyzer, vibrating sample magnetometer and X-ray diffractometer (XRD). The heating efficiency of the CA-SPIONs was investigated by a high frequency induction heater. The transverse relaxivity (r2) of the CA-SPIONs was evaluated by a 3.0 T MRI scanner. RESULTS: The CA-SPIONs prepared were dispersed well in water with a dark black color and had good magnetic responsiveness. The CA-SPIONs were spherical in shape and uniform in size with an average size around 12 nm. The hydrodynamic average size of the CA-SPIONs was (72.35±4.47) nm with a polydispersity index of 0.231 ± 0.029. The result of infrared spectrum indicated that CA was successfully modified to the surface of SPIONs. The result of thermogravimetric analysis showed that the weight percentage of CA modified on the CA-SPIONs was 9.0%. The result of magnetic property evaluation demonstrated that the CA-SPIONs exhibited excellent superparamagetism with a saturation magnetism of 63.58 emu/g. The XRD result indicated that the CA-SPIONs were in inverse spinel structure. The crystallite size of the CA-SPIONs was calculated to be 12.4 nm by Debye-Scherrer equation. Under the high frequency alternating electromagnetic field with electric current of 9 A and frequency ranging from 45 to 50 kHz, the CA-SPIONs exhibited excellent heating efficiency and the specific absorption rate (SAR) value was calculated to be 26 W/g. The r2 of the CA-SPIONs was assessed to be 338 (mmol/L)^-1×s^-1 by a 3.0 T MRI scanner, which suggested the excellent negative contrast enhancement effect of the CA-SPIONs. CONCLUSION The CA-SPIONs are expected to be used as a promising agent for magnetic targeting, hyperthermia and MRI detection.
Citric Acid ; Contrast Media ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Nanoparticles ; Particle Size ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
Aged ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Methylation ; Middle Aged ; Muscle Proteins/metabolism* ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Progression-Free Survival ; Prostatectomy ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

This paper collected the traditional Chinese medicine (TCM) prescriptions of osteoporosis and osteoarthritis from CNKI to set up database and used TCM inheritance system to analyze the composing principles in prescriptions. We collected 103 and 106 prescriptions for osteoporosis and osteoarthritis respectively, then analyzed inherent principles between herbs in prescriptions by using the TCM inheritance system, and obtained the frequency of each herb, and drug combinations of two diseases' prescriptions. The result showed that the principles in TCM prescriptions of osteoporosis and osteoarthritis are similarities, buch as tonifying kidney and invigorating the circulation of blood, but differences of the specific drugs. That is to say, tonifying kidney is the main method of osteoporosis treatment, however, invigorating the circulation of blood is the main method of osteoarthritis treatment.
Blood Circulation ; drug effects ; Databases, Factual ; Drug Prescriptions ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Kidney ; drug effects ; physiopathology ; Osteoarthritis ; drug therapy ; physiopathology ; Osteoporosis ; drug therapy ; physiopathology

OBJECTIVESix1 and Six4 are expressed in several tumors, and associated with tumor progress and poor prognosis. The aim of this study was to investigate the expression of Six1 and Six4 in esophageal squamous cell carcinoma (ESCC), and to evaluate their correlation with the clinicopathological factors and prognosis.

METHODSTissue microarray technology and immunohistochemical method (EnVision) were used to detect the expression of Six1 and Six4 in the tumor tissues and corresponding adjacent normal epithelium of esophagus from 292 ESCC patients.

RESULTSAmong the 292 ESCC patients, the positive rates of Six1 and Six4 protein expression in tumor tissues were 72.9% (213/292) and 56.2% (164/292), respectively, significantly higher than the expression rate of 33.2% (97/292) and 32.5% (95/292) in adjacent normal epithelium of esophagus (P < 0.05). Chi square test showed that the expression of Six1 protein was related to tumor size, depth of tumor invasion and patient survival status; higher Six4 protein expression level was related to poor differentiation and increased depth of invasion. Single factor Log-rank analysis revealed that gender, TNM stage, Six1 protein expression level were related to the overall survival of ESCC patients (P < 0.05), while the five-year survival rate was significantly higher in the Six1-negative group than the Six1-positive group [51.9% (41/79) vs. 43.7% (93/213)]. Multi-factor Cox proportional risk model analysis showed that TNM stage and positive expression of Six1 were independent prognostic factors for ESCC patients (P < 0.05).

CONCLUSIONSSix1 and Six4 are highly expressed in ESCC. Their expression levels are closely related to the progress and prognosis of ESCC. Over-expression of Six1 is related to poor prognosis in ESCC patients. Thus, Six1 could be used as an important prognostic indicator for ESCC patients.

Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Esophageal Neoplasms ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Homeodomain Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Survival Rate ; Trans-Activators ; metabolism ; Tumor Burden