Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

ObjectiveTo establish the fingerprint of seven commercially available Yangyin Qingfei preparations， to quantitatively analyze the index components， to evaluate their quality uniformity with multivariate statistical analysis， and to explore the quality differences among different dosage forms. MethodA total of 33 batches of commercially available 7 kinds of Yangyin Qingfei preparations were analyzed by high performance liquid chromatography（HPLC）， the fingerprints were established and the common peaks were identified. Paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol were selected as the indicators of quality attributes to quantitatively analyze 33 batches of preparations. Based on the administration methods of Yangyin Qingfei preparations， the daily intake was calculated and the radar charts were poltted， and cluster analysis and principal component analysis were used to explore the quality differences of 7 kinds of Yangyin Qingfei preparations and the quality uniformity among different batches of the same dosage form. ResultThe similarity of fingerprints of 7 dosage forms was 0.248-0.956， suggesting that there were significant differences among different dosage forms of Yangyin Qingfei preparations， and a total of 15 common peaks were calibrated， of which peak 7， peak 8， peak 11， peak 13 and peak 15 were paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol， respectively. The radar plots showed that the average total daily intake of large honeyed pills and water honeyed pills was the highest， and the uniformity of pill components was better. The quality of 33 batches of samples was divided into poor quality and high quality by cluster analysis. Principal component analysis showed that the uniformity and dosage form of different dosage forms were significantly different， the oral liquid had the best quality homogeneity with the minimum dispersion. And the content of paeonol in different dosage forms was significantly different， which was the key component of quality control of Yangyin Qingfei preparations. ConclusionYangyin Qingfei large honeyed pills and water honeyed pills show high content and good uniformity， which are relatively preferred dosage forms. Different preparation processes have a great influence on the content of paeonol， and its quality control should be emphasized during production. This study provides a scientific method for the comparison of product quality of different dosage forms of traditional Chinese medicine prescriptions， which is helpful for the development of preferred dosage forms of different prescriptions， and provides a reference for efficient use of medication in the clinical practice.

Objective To summarize the clinical registration data of endodontic diseases registered in ClinicalTri-als.gov in the United States and Chinese Clinical Trial Registry(ChiCTR),and analyze the registration characteristics at home and abroad.Methods We searched the clinical studies related to endodontic disease registered in the two data-bases from January 1,2000,to August 20,2023.We extracted and analyzed the information from clinical studies relat-ed to endodontic diseases.The extracted content included information on the registration region,registration year,trial title,research direction,sample size,trial progress,study type,trial design,blinding method,clinical trial phase,and participating institutions.Results The two databases contained a total of 536 191 registered items,of which 634 were endodontic diseases.Clinical trials in the registry of endodontic diseases involved 43 countries,of which the top three were Egypt(188 items),China(130 items),and the America(46 items).In addition,the number of registrations of clini-cal trials on endodontic diseases has significantly increased since 2015.The research directions were mainly pulposis(434 items),caries(106 items),and periapical diseases(77 items),which mostly involved etiology,drug intervention,surgical intervention,new technology,and new materials.Moreover,there were 430 clinical trials(67.82%)with a sam-ple size<100 and 185(29.18%)with a sample size of 100-999.The progress status at the time of registration showed the largest number of completed trials,accounting for 286 items(45.11%),followed by unknown(125 items),recruiting(110 items),and not yet recruiting(81 items).The main research types were intervention studies(546 items,86.12%),and the main design model was randomized parallel controlled trials(473 items,74.61%).Additionally,423 items(66.72%)were marked using the blind method,mainly double-blind trials(195 items),followed by other/unmarked(123 items,19.40%)and open study(88 items,13.88%).Furthermore,the largest number of items in the study phase were marked other/unlabeled(388 items),followed by phaseⅡ study(69 items)and preliminary study(62 items).Addi-tionally,611 items(96.37%)were clinical trials with a number of participating institutions<3,and 23 items(3.63%)had a number of participating institutions≥3.Conclusion The number of clinical trials registered for endodontic dis-eases is generally on the rise,but it is still relatively small.The quality of the study design needs to be enhanced,and the registration information in the study phase needs to be improved.Moreover,the number of multicenter trials is small.In the future,we should fully mobilize the talent advantages of well-known stomatology majors in China,take the lead in conducting high-quality,multi-center clinical research,and realize the transformation of results.

Objective To analyze the effects of probiotics combined with montmorillonite powder on intestinal mucosa and expressions of intestinal microorganism function-related genes in neonatal rats with rotavirus(RV)infection.Methods RV infection model was established by intragastric administration of SA11 strain rotavirus.Forty-eight suckling rats were randomly divided into normal group(0.9％NaCl),model group(0.9％NaCl),experimental group(0.06 g·mL-1 montmorillonite powder)and combined group(0.06 g·mL-1 montmorillonite powder+6.5 × 107 CFU·mL-1 Saccharomyces cerevisiae powder)with 12 rats in each group.The feces were collected for evaluation.The levels of serum tumor necrosis factor-a(TNF-a),interleukin-1 β(IL-1 β)and IL-17 were detected by enzyme-linked immunosorbent assay,the levels of aquaporin(AQP)in intestinal tissues was detected by real-time fluorescence quantitative polymerase chain reaction,and the counts of Bifidobacteria and Escherichia coli in feces were detected by bacterial 16srDNA fluorescence quantitative polymerase chain reaction.Results The feces scores in normal,model,experimental and combined groups were(1.01±0.10),(2.97±0.08),(2.84±0.03)and(2.77±0.03)points;TNF-α levels were(132.54±14.63),(185.66±19.64),(165.25±17.63)and(149.95±15.76)pg·mL-1;IL-1β levels were(172.32±18.68),(265.34±27.72),(202.34±21.34)and(186.24±19.46)pg·mL-1;IL-17 levels were(118.62±12.44),(173.24±18.25),(152.32±16.72)and(122.54±13.58)pg·mL-1;Bifidobacteria counts were(6.35±0.64),(4.31±0.44),(4.93±0.50)and(5.34±0.54)CFU·g-1;Escherichia coli counts were(6.14±0.62),(8.78±0.88),(8.46±0.85)and(8.12±0.83)CFU·g-1;mRNA levels of AQP2 were 1.02±0.05,0.72±0.07,0.89±0.08 and 1.21±0.12;mRNA expression levels of AQP4 were 1.04±0.07,0.42±0.05,0.78±0.08 and 1.19±0.12;mRNA expression levels ofAQP8 were 1.00±0.06,0.63±0.06,0.91±0.09 and 1.30±0.13,respectively.There were significant differences of above indexes between the model group with the normal,experimental and combined groups(all P＜0.05).Conclusion Montmorillonite powder combined with probiotics can improve fecal properties,reduce serum inflammatory factors and correct intestinal flora disorders in neonatal rats with RV infection,which may be related to improving the expressions of intestinal A QP2,AQP4 and AQP8.