Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism* ; Panax/physiology* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Phospholipase D/metabolism* ; Plants, Medicinal/enzymology* ; Germination ; Multigene Family ; Water/metabolism* ; Dehydration ; Phylogeny

Based on whole-genome identification of the TPS gene family in Perilla frutescens and screening, cloning, bioinformatics, and expression analysis of the synthetic enzyme for the insect-resistant component germacrene D, this study lays the foundation for understanding the biological function of the TPS gene family and the insect resistance mechanism in P. frutescens. This study used bioinformatics tools to identify the TPS gene family of P. frutescens based on its whole genome and predicted the physicochemical properties, systematic classification, and promoter cis-elements of the proteins. The relative content of germacrene D was detected in both normal and insect-infested leaves of P. frutescens, and the germacrene D synthase was screened and isolated. Gene cloning, bioinformatics analysis, and expression profiling were then performed. The results showed that a total of 99 TPS genes were identified in the genome, which were classified into the TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g subfamilies. Conserved motif analysis showed that the TPS in P. frutescens has conserved structural characteristics within the same subfamily. Promoter cis-element analysis predicted the presence of light-responsive elements, multiple hormone-responsive elements, and stress-responsive elements in the TPS family of P. frutescens. Transcriptome data revealed that most of the TPS genes in P. frutescens were highly expressed in the leaves. GC-MS analysis showed that the relative content of germacrene D significantly increased in insect-damaged leaves, suggesting that it may act as an insect-resistant component. The germacrene D synthase gene was screened through homologous protein binding gene expression and was found to belong to the TPS-a subfamily, encoding a 64.89 kDa protein. This protein was hydrophilic, lacked a transmembrane structure and signal peptide, and was predominantly expressed in leaves, with significantly higher expression in insect-damaged leaves compared to normal leaves. In vitro expression results showed that germacrene D synthase tended to form inclusion bodies. Molecular docking showed that farnesyl pyrophosphate(FPP) fell into the active pocket of the protein and interacted strongly with six active sites. This study provides a foundation for further research on the biological functions of the TPS gene family in P. frutescens and the molecular mechanisms underlying its insect resistance.
Perilla frutescens/chemistry* ; Plant Proteins/chemistry* ; Multigene Family ; Sesquiterpenes, Germacrane/metabolism* ; Alkyl and Aryl Transferases/chemistry* ; Phylogeny ; Gene Expression Regulation, Plant

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.

OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Objective To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy(SMA).Methods A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024.Results Compared with the baseline data,67%(8/12),74%(35/47),and 74%(35/47)of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders,Hammersmith Functional Motor Scale Expanded,and Revised Upper Limb Module,respectively,and the distance of 6-minute walking test increased from 207.00(179.00,281.50)meters to 233.00(205.25,287.50)meters(P<0.05)after nusinersen sodium treatment.Of all 50 children with SMA,24(48%)showed good tolerability after administration,with no significant or persistent abnormalities observed in 2 034 laboratory test results,and furthermore,there were no serious or immunological adverse events related to the treatment.After treatment,there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction,as well as a significant change in the level of 25-(OH)vitamin D in 15 children with vitamin D deficiency(P<0.05).Conclusions For children with SMA,treatment with nusinersen sodium can continuously improve the response rates of motor function scales,with good tolerability and safety.