ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

This study investigated the infection status,drug resistance,and molecular characteristics of Shiga toxin-producing Escherichia coli(STEC)in domestic goats in Chengkou county,Chongqing.In August 2023,283 fecal samples were collected from households in Chengkou county.After enrichment with EC broth and inoculation onto selective media,samples that tested positive for stx1/stx2 were selected for further isolation.The positive strains were investigated with antimicrobial susceptibility testing and whole genome sequencing.According to the whole genomic sequences,the stx subtypes,serotypes,multi-locus sequence types,virulence genes,drug resistance genes,and phylogenetic relationships of the STEC strains were analyzed.Forty-six strains of STEC were isolated from 283 goat fecal samples,thus resulting in a detection rate of 16.25%.The 46 STEC strains were categorized into 12 O∶H serotypes,among which O76∶H19 and O8∶H7 predominated,each represented by 9 strains.Five STEC strains were identified as serotype O157∶H7.The 46 STEC strains were categorized into 11 sequence types(STs),among which ST675 and ST196 predominated,each represented by nine strains,accounting for a 19.57%proportion.The strains were categorized into 7 stx subtypes,among which stx1c(26/46,56.52%),followed by stx2k(9/46,19.57%)predominated.All nine Stx2k-STEC strains were identified as serotype O8∶H7 and sequence type ST196.In antimicrobial susceptibility testing,2 STEC strains were resistant to ampicillin,one strain was resistant to ampicillin/sulbactam,one strain was resistant to cefazolin,and one strain was resistant to cefoxitin.Nine Stx2k-STEC strains were found to carry the beta-lactam resistance gene blaEC-18.Antimicrobial sensitivity tests revealed that the nine Stx2k-STEC strains were sensitive to all 15 tested antibiotics.Moreover,phylogenetic analysis indicated that the 9 Stx2k-STEC strains were remarkably similar but showed high genetic diversity with respect to that of the Stx2k-STEC strains isolated from other regions in China.Goatsare an important animal reservoir for STEC in theChengkou district of Chongqing,and novel sequence type Stx2k-STEC strains distinct from those found in other regions of China were identified in this region.

Objective:To explore the neuroprotective effect of α7 nicotinic acetylcholine receptor (α7nAChR) on rat models of Parkinson's disease (PD) and its underlying mechanism.Methods:Forty-eight 8-week-old SPF-grade SD rats were randomly divided into a normal control group, a PD model group, an α7nAChR empty vector group and an α7nAChR overexpression group, with 12 rats in each group. PD models in the latter 3 groups of rats were established by 6-hydroxydopamine (6-OHDA). Four weeks after modeling, rats in the latter 2 groups were injected with 2 μL α7nAChR overexpression lentivirus or empty vector lentivirus through stereotactic intracerebral injection, while rats in the normal control group did not receive any treatment. Two weeks after injection, the behavioral changes of these rats were detected by apomorphine-induced rotation test; the right substantia nigra pars compacta (SNc) was prepared and performed the following experiments: hematoxylin-eosin (HE) staining and Nissl staining were used to detect the neuron morphological changes, TUNEL was used to detect the neuron apoptosis, fluorescent double labeling was used to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-Syn), ELISA was used to detect the expressions of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and Western blotting was used to detect the expressions of ferroptosis-related proteins (ferritin heavy chain 1 [FTH1], Sigma receptor 1 [S1R], glutathione peroxidase 4 [GPX4], long chain acyl-coa synthetase 4 [ACSL4], solute carrier family 7 member11 [SLC7A11]), and the expressions of proteins related to CAMKII/ERK pathway (phosphorylated calmodulin kinase Ⅱ [p-CAMK Ⅱ], phosphorylated extracellular signal regulated kinase [p-ERK], and phosphorylated Kirsten rat sarcoma viral oncogene homolog [p-KRAS]).Results:(1) Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly larger number of rotations ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly smaller number of rotations ( P<0.05). (2) HE staining and Nissl staining showed that the PD model group had decreased number of dopaminergic neurons and Nissl bodies, accompanied by neuronal distribution disorder, nuclear condensation or swelling; the α7nAChR-overexpression group had obviously improved appearance of dopaminergic neurons, with normal morphology and less cell degeneration. (3) TUNEL results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group, and α7nAChR overexpression group had significantly higher apoptosis rate ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had statistically lower apoptosis rate ( P<0.05). (4) Double immunofluorescent staining results showed that compared with the normal control group (303.61±48.40, 13 985.80±1 956.06), the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased α-Syn expression (4 310.40±518.43, 3 846.60±524.47 and 1 033.55±59.98) and statistically decreased TH expression (760.97±57.26, 842.55±113.41 and 8 101.82±1 171.85) in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased α-Syn expression and increased TH expression in the right SNc ( P<0.05). (5) ELISA results showed that the 4-HNE and MDA expressions in the right SNc of the PD model group, α7nAChR empty vector group and α7nAChR overexpression group were significantly higher than those in the normal control group ( P<0.05); the 4-HNE and MDA expressions in the α7nAChR overexpression group were significantly lower than those in the PD model group ( P<0.05). (6) Western blotting results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly decreased FTH1, S1R, GPX4, and SLC7A11 protein expressions, and statistically increased ACSL4 protein expression in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly increased FTH1, S1R, GPX4, and SLC7A11 protein expressions and decreased ACSL4 protein expression in the right SNc ( P<0.05). Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05). Conclusion:The α7nAChR may exert neuroprotective effect on PD rat models by regulating the CAMKII/ERK pathway and ferroptosis-related proteins.

Objective:To identify the developmental trajectories of internet use and well-being among the elderly in China,and to explore the dynamic relationship between these trajectories and the moderating role of intergenerational support from children.Methods:Group-Based Trajectory Modeling was employed to identify developmental trajectories,and moderated generalized logits models were used to analyze the relationship between trajectories and the moderating effect of intergenerational support from children.Results:Both internet use and well-being among the elderly exhibited differentiated developmental trajectories.Internet use trajectories had a significant positive impact on well-being trajectories.Compared with the low-level group,the elderly in the moderate internet use group being classified into the medium-and high-level well-being groups were 1.550 times(P<0.01)and 1.539 times(P<0.05)those of the offline group respectively,while those in the high-frequency internet use group were 9.560 times(P<0.01)and 9.030 times(P<0.01),respectively.Intergenerational support from children negatively moderated this relationship(medium-level well-being group:OR=0.768,P<0.05;high-level well-being group:OR=0.733,P<0.05).Conclusions:Internet use can sustainably enhance the well-being of the elderly over the long term,with this effect being more pronounced among those receiving less intergenerational support from children.It is recommended to establish a dual-track service system integrating online and offline channels,and to prioritize internet empowerment as a targeted social support strategy for the elderly with insufficient intergenerational support from children.

Objective:To identify the developmental trajectories of internet use and well-being among the elderly in China,and to explore the dynamic relationship between these trajectories and the moderating role of intergenerational support from children.Methods:Group-Based Trajectory Modeling was employed to identify developmental trajectories,and moderated generalized logits models were used to analyze the relationship between trajectories and the moderating effect of intergenerational support from children.Results:Both internet use and well-being among the elderly exhibited differentiated developmental trajectories.Internet use trajectories had a significant positive impact on well-being trajectories.Compared with the low-level group,the elderly in the moderate internet use group being classified into the medium-and high-level well-being groups were 1.550 times(P<0.01)and 1.539 times(P<0.05)those of the offline group respectively,while those in the high-frequency internet use group were 9.560 times(P<0.01)and 9.030 times(P<0.01),respectively.Intergenerational support from children negatively moderated this relationship(medium-level well-being group:OR=0.768,P<0.05;high-level well-being group:OR=0.733,P<0.05).Conclusions:Internet use can sustainably enhance the well-being of the elderly over the long term,with this effect being more pronounced among those receiving less intergenerational support from children.It is recommended to establish a dual-track service system integrating online and offline channels,and to prioritize internet empowerment as a targeted social support strategy for the elderly with insufficient intergenerational support from children.

This study investigated the infection status,drug resistance,and molecular characteristics of Shiga toxin-producing Escherichia coli(STEC)in domestic goats in Chengkou county,Chongqing.In August 2023,283 fecal samples were collected from households in Chengkou county.After enrichment with EC broth and inoculation onto selective media,samples that tested positive for stx1/stx2 were selected for further isolation.The positive strains were investigated with antimicrobial susceptibility testing and whole genome sequencing.According to the whole genomic sequences,the stx subtypes,serotypes,multi-locus sequence types,virulence genes,drug resistance genes,and phylogenetic relationships of the STEC strains were analyzed.Forty-six strains of STEC were isolated from 283 goat fecal samples,thus resulting in a detection rate of 16.25%.The 46 STEC strains were categorized into 12 O∶H serotypes,among which O76∶H19 and O8∶H7 predominated,each represented by 9 strains.Five STEC strains were identified as serotype O157∶H7.The 46 STEC strains were categorized into 11 sequence types(STs),among which ST675 and ST196 predominated,each represented by nine strains,accounting for a 19.57%proportion.The strains were categorized into 7 stx subtypes,among which stx1c(26/46,56.52%),followed by stx2k(9/46,19.57%)predominated.All nine Stx2k-STEC strains were identified as serotype O8∶H7 and sequence type ST196.In antimicrobial susceptibility testing,2 STEC strains were resistant to ampicillin,one strain was resistant to ampicillin/sulbactam,one strain was resistant to cefazolin,and one strain was resistant to cefoxitin.Nine Stx2k-STEC strains were found to carry the beta-lactam resistance gene blaEC-18.Antimicrobial sensitivity tests revealed that the nine Stx2k-STEC strains were sensitive to all 15 tested antibiotics.Moreover,phylogenetic analysis indicated that the 9 Stx2k-STEC strains were remarkably similar but showed high genetic diversity with respect to that of the Stx2k-STEC strains isolated from other regions in China.Goatsare an important animal reservoir for STEC in theChengkou district of Chongqing,and novel sequence type Stx2k-STEC strains distinct from those found in other regions of China were identified in this region.

Objective:To explore the neuroprotective effect of α7 nicotinic acetylcholine receptor (α7nAChR) on rat models of Parkinson's disease (PD) and its underlying mechanism.Methods:Forty-eight 8-week-old SPF-grade SD rats were randomly divided into a normal control group, a PD model group, an α7nAChR empty vector group and an α7nAChR overexpression group, with 12 rats in each group. PD models in the latter 3 groups of rats were established by 6-hydroxydopamine (6-OHDA). Four weeks after modeling, rats in the latter 2 groups were injected with 2 μL α7nAChR overexpression lentivirus or empty vector lentivirus through stereotactic intracerebral injection, while rats in the normal control group did not receive any treatment. Two weeks after injection, the behavioral changes of these rats were detected by apomorphine-induced rotation test; the right substantia nigra pars compacta (SNc) was prepared and performed the following experiments: hematoxylin-eosin (HE) staining and Nissl staining were used to detect the neuron morphological changes, TUNEL was used to detect the neuron apoptosis, fluorescent double labeling was used to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-Syn), ELISA was used to detect the expressions of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and Western blotting was used to detect the expressions of ferroptosis-related proteins (ferritin heavy chain 1 [FTH1], Sigma receptor 1 [S1R], glutathione peroxidase 4 [GPX4], long chain acyl-coa synthetase 4 [ACSL4], solute carrier family 7 member11 [SLC7A11]), and the expressions of proteins related to CAMKII/ERK pathway (phosphorylated calmodulin kinase Ⅱ [p-CAMK Ⅱ], phosphorylated extracellular signal regulated kinase [p-ERK], and phosphorylated Kirsten rat sarcoma viral oncogene homolog [p-KRAS]).Results:(1) Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly larger number of rotations ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly smaller number of rotations ( P<0.05). (2) HE staining and Nissl staining showed that the PD model group had decreased number of dopaminergic neurons and Nissl bodies, accompanied by neuronal distribution disorder, nuclear condensation or swelling; the α7nAChR-overexpression group had obviously improved appearance of dopaminergic neurons, with normal morphology and less cell degeneration. (3) TUNEL results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group, and α7nAChR overexpression group had significantly higher apoptosis rate ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had statistically lower apoptosis rate ( P<0.05). (4) Double immunofluorescent staining results showed that compared with the normal control group (303.61±48.40, 13 985.80±1 956.06), the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased α-Syn expression (4 310.40±518.43, 3 846.60±524.47 and 1 033.55±59.98) and statistically decreased TH expression (760.97±57.26, 842.55±113.41 and 8 101.82±1 171.85) in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased α-Syn expression and increased TH expression in the right SNc ( P<0.05). (5) ELISA results showed that the 4-HNE and MDA expressions in the right SNc of the PD model group, α7nAChR empty vector group and α7nAChR overexpression group were significantly higher than those in the normal control group ( P<0.05); the 4-HNE and MDA expressions in the α7nAChR overexpression group were significantly lower than those in the PD model group ( P<0.05). (6) Western blotting results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly decreased FTH1, S1R, GPX4, and SLC7A11 protein expressions, and statistically increased ACSL4 protein expression in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly increased FTH1, S1R, GPX4, and SLC7A11 protein expressions and decreased ACSL4 protein expression in the right SNc ( P<0.05). Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05). Conclusion:The α7nAChR may exert neuroprotective effect on PD rat models by regulating the CAMKII/ERK pathway and ferroptosis-related proteins.