Objective: To investigate the trend in disease burden of asthma attributable to tobacco in China from 1990 to 2021, so as to provide the basis for improving intervention measures of asthma. Methods: Data on asthma-related mortality and disability-adjusted life years (DALY) attributable to tobacco among adults aged ≥30 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Age-standardized mortality and age-standardized DALY rate were calculated using the GBD world standard population structure to analyze the tobacco-attributable asthma burden. The average annual percent change (AAPC) was employed to evaluate temporal trends in the age-standardized mortality and DALY rate from 1990 to 2021. Results: In China, the age-standardized mortality and age-standardized DALY rate of asthma attributable to tobacco decreased from 0.73/100 000 and 22.20/100 000 in 1990 to 0.17/100 000 and 6.64/100 000 in 2021, showing downward trends (AAPC=-4.603% and -3.888%, both P<0.05). Among males, the tobacco-attributable age-standardized mortality and age-standardized DALY rate declined from 1.44/100 000 and 41.05/100 000 in 1990 to 0.36/100 000 and 12.79/100 000 in 2021 (AAPC=-4.369% and -3.810%, both P<0.05). Among females, the corresponding rates decreased from 0.21/105 and 5.37/105 to 0.03/105 and 1.08/105 (AAPC=-6.074% and -5.074%, both P<0.05). In 2021, males had higher tobacco-attributable age-standardized mortality and age-standardized DALY rate for asthma than females. Both the mortality and DALY rate of asthma attributable to tobacco increased with age, peaking in the age group ≥80 years at 7.84/100 000 and 112.07/100 000, respectively. Conclusion From 1990 to 2021, the disease burden of asthma attributable to tobacco showed a declining trend in China, with males and elderly population aged ≥80 years bearing a relatively heavier disease burden.

Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.

Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.

"Yang Wei Yin Xian" originates from "Jin Kui Yao Lue". It denotes the slight pulse at the cun pulse and the yin pulse in the yang position, which indicates a deficiency of yang qi in the upper focus. The ulnar vein is a cord, and the yin position corresponds to the yin vein, which is excessive yin pathogen in the lower jiao. Lung cancer complicated with sepsis is common in clinical practice; it is characterized by a high mortality rate and poor conventional treatment outcomes. This article discusses "Yang Wei Yin Xian" and its relationship with lung cancer complicated by sepsis, evaluates the selection of TCM prescriptions and efficacy mechanisms of "Yang Wei Yin Xian" theory, and provides a reference for the use of this theory to guide clinical treatment.

This study explored the prescription pattern of traditional Chinese medicine(TCM) in the treatment of hypertensive left ventricular hypertrophy(LVH), so as to provide a relevant theoretical basis for the clinical diagnosis and treatment of hypertensive LVH. The study systematically searched the databases of CNKI, Wanfang, VIP, and SinoMed to screen out the qualified literature on TCM treatment of hypertensive LVH and used Microsoft Excel 2021 to establish the relevant prescription database. It also counted the frequency, property, flavor, and meridian affiliation of TCM in the prescriptions and classified their efficacy. The study used Lantern 5.0 and Rstudio software to analyze the hidden structural models and association rules of the high-frequency TCM with a frequency of >3.50% and adopted Origin 2024 software to visualize the data, so as to explore the prescription pattern of TCM in treating hypertensive LVH. The results showed that a total of 128 TCM prescriptions were included, involving 163 TCM with a total frequency of 1 242. The high-frequency TCM included Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Gastrodiae Rhizoma, Poria, and Chuanxiong Rhizoma, with the main efficacy from blood-activating and stasis-resolving herbs, tonic herbs, and liver-calming and wind-extinguishing herbs. The latent structure analysis(LSA) identified 10 latent variables, 20 latent classes, 7 comprehensive clustering models, and 23 core prescriptions. It was speculated that the common syndromes of hypertensive LVH included blood stasis obstructing the collaterals, ascending hyperactivity of liver Yang, Yin deficiency with Yang hyperactivity, and intermingled phlegm and blood stasis. The association rule analysis yielded 33 strong association rules, with the highest comprehensive association rule being Gastrodiae Rhizoma→Uncariae Ramulus Cum Uncis. Hypertensive LVH is characterized by asthenia in origin and asthenia in superficiality, with Yin deficiency and Qi deficiency as the origin and blood stasis and phlegm as the superficiality. Clinical treatment focuses on activating blood circulation, resolving stasis, tonifying Qi, and nourishing Yin, combined with syndrome-specific therapies such as calming wind and stopping convulsions, clearing heat, eliminating dampness and resolving phlegm, and promoting diuresis and reducing swelling.
Drugs, Chinese Herbal/therapeutic use* ; Data Mining ; Humans ; Hypertension/complications* ; Hypertrophy, Left Ventricular/physiopathology* ; Medicine, Chinese Traditional ; Drug Prescriptions

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Repeated transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation techniques. In order to investigate the effects of rTMS on the excitability of different types of neurons, this study is conducted to investigate the effects of rTMS on the cognitive function of mice and the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons from the perspective of electrophysiology. In this study, mice were randomly divided into glutaminergic control group, glutaminergic magnetic stimulation group, gamma-aminobutyric acid energy control group, and gamma-aminobutyric acid magnetic stimulation group. The four groups of mice were injected with adeno-associated virus to label two types of neurons and were implanted optical fiber. The stimulation groups received 14 days of stimulation and the control groups received 14 days of pseudo-stimulation. The fluorescence intensity of calcium ions in mice was recorded by optical fiber system. Behavioral experiments were conducted to explore the changes of cognitive function in mice. The patch-clamp system was used to detect the changes of neuronal action potential characteristics. The results showed that rTMS significantly improved the cognitive function of mice, increased the amplitude of calcium fluorescence of glutamergic neurons and gamma-aminobutyric neurons in the hippocampus, and enhanced the action potential related indexes of glutamergic neurons and gamma-aminobutyric neurons. The results suggest that rTMS can improve the cognitive ability of mice by enhancing the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons.
Animals ; Mice ; Hippocampus/cytology* ; Transcranial Magnetic Stimulation ; Neurons/physiology* ; Male ; Cognition/physiology* ; gamma-Aminobutyric Acid/metabolism* ; Action Potentials/physiology*

To address the challenges in blood cell recognition caused by diverse morphology, dense distribution, and the abundance of small target information, this paper proposes a blood cell detection algorithm - the "You Only Look Once" model based on hybrid mixing attention and deep over-parameters (HADO-YOLO). First, a hybrid attention mechanism is introduced into the backbone network to enhance the model's sensitivity to detailed features. Second, the standard convolution layers with downsampling in the neck network are replaced with deep over-parameterized convolutions to expand the receptive field and improve feature representation. Finally, the detection head is decoupled to enhance the model's robustness for detecting abnormal cells. Experimental results on the Blood Cell Counting Dataset (BCCD) demonstrate that the HADO-YOLO algorithm achieves a mean average precision of 90.2% and a precision of 93.8%, outperforming the baseline YOLO model. Compared with existing blood cell detection methods, the proposed algorithm achieves state-of-the-art detection performance. In conclusion, HADO-YOLO offers a more efficient and accurate solution for identifying various types of blood cells, providing valuable technical support for future clinical diagnostic applications.
Algorithms ; Humans ; Blood Cells/cytology* ; Blood Cell Count/methods* ; Neural Networks, Computer ; Deep Learning ; Detection Algorithms

⁶⁰Co-γ ray irradiation has the unique advantages of high efficiency， strong penetration， operation at room temperature and no residue， which has been widely used in the sterilization of Chinese medicinal materials， decoction pieces， Chinese patent medicine. However， the irradiation effect may cause changes in the content of chemical components in Chinese materia medica or the emergence of new radiolysis products， leading to reduced efficacy and uncontrollable safety risks. This paper reviewed the relevant literature at home and abroad， summarized the effect of irradiation sterilization on various types of chemical compositions of Chinese medicinal materials and their preparations， and analyzed and explored the rule of change. The results showed that the content changes of various chemical components in Chinese materia medica after ⁶⁰Co-γ ray irradiation sterilization varied. The contents of most flavonoids， terpenoids， phenylpropanoids and quinones decreased after irradiation， and the degree of decrease increased with the elevated irradiation dose. The contents of lignans， alkaloids， isoflavones and some terpenoids did not change significantly before and after irradiation， while the content changes of triterpenoid saponins， dihydroflavonols， chalcones， sugars and glycosides after irradiation were not yet uniform. Therefore， it is recommended to pay attention to the compositional changes of irradiated Chinese medicines， strengthen the research on the standards of irradiated Chinese medicines， and standardize the irradiation and sterilization of Chinese medicines in order to promote the healthy and rational application of irradiated Chinese medicines.