Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

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*

Recently,the theoretical system and practical path for the deep integration of digitalization and traditional industrialization have gradually matured.Medical innovation and digital technology are progressing,and the deep integration of intensive care medicine and intelligence is surpassing the traditional informatization and ushering in new development opportunities.Technologies such as 5G,big data,artificial intelligence,and digital twins can help to understand more complex critical care issues,improve the diagnoses and prediction of diseases and symptoms,develop more accurate treatment strategies,and even transform the service model of critical care medicine.This paper summarizes the application and challenge of digital technology in the practical scenarios of critical care medicine,so as to further consolidate infrastructure,enrich application scenarios,accelerate implementation,improve effectiveness,and strengthen the safety and compliance with the regulations.

Objective To investigate the protective effect and mechanism of heat acclimation(HA)on electromagnetic field(EMF)induced hippocampus neuron injury in mice.Methods Forty healthy BALB/c male mice(18～22 g,7 weeks old)were randomly divided into 4 groups(n=10):Control group(Con),HA group(34℃,30 d),EMF group(2 450 MHz,20 min/d,4 weeks)and HA+EMF group(HA preconditioning+EMF).Sucrose preference test was performed to evaluate sucrose preference levels of mice in each group.Tail suspension test and forced swimming test were utilized to observe the immobility time.Morris water maze test was conducted to determine the learning and memory capabilities.Pathological changes in the hippocampus were observed with HE staining.Immunohistochemical assay for Iba1(marker of microglia),CD68(marker of pro-inflammatory phenotype)and CD206(marker of anti-inflammatory phenotype)were used to detect the number and activation phenotype of microglia in the hippocampus.ELISA was applied to measure the levels of TNF-α,IL-1β,TGF-β and IL-10 in the hippocampus of each group.Western blotting was performed to determine the protein levels of HSP70 in the hippocampus.Results As compared with the Con group,the EMF group showed a decreased preference for sucrose(P<0.05),prolonged immobile time in the tail suspension test(P<0.01)as well as in the forced swimming test(P<0.01),extented escape latency on the 7th day(P<0.01),and a decreased time of crossing the platform(P<0.05).EMF exposure resulted in that the hippocampal neurons were in disordered arrangement,loose structure and irregular morphology,with swollen cytoplasm and condensed nuclei,swollen and more microglial cells in the hippocampus(P<0.01),and enhanced relative fluorescence intensity of CD68(P<0.01),but not in CD206 fluorescence intensity(P=0.885).All these findings suggested that activated microglia predominantly exhibited a pro-inflammatory M1 phenotype during this phase.In the hippocampus,the levels of TNF-α and IL-1β were significantly increased,while the levels of IL-10 and TGF-β were significantly decreased(P<0.01).HA treatment reversed the conditions induced by EMF exposure,including better preference for sucrose(P<0.01),shorten immobile time in tail suspension test(P<0.05)and forced swimming test(P<0.01),less escape latency on the 7th day(P<0.01),and improved hippocampal cell injuries.Compared with the Con group,there were more microglial cells in the hippocampus in the HA+EMF group,with increased relative fluorescence intensity of M2 phenotype marker CD206(P<0.01)and decreased CD68 fluorescence intensity(P<0.01).HA treatment also significantly decreased the expression of TNF-α and IL-1β levels(P<0.01),increased the expression of IL-10 and TGF-β(P<0.01),and elevated the protein level of HSP70(P<0.01)when compared with the EMF group.Conclusion HA may ameliorate EMF-induced hippocampus neurons injury in mice by altering the phenotype of activated microglia and inhibiting inflammatory responses.

A new method was developed for simultaneous and efficient determination of linear perfluorooctanoic acid(n-PFOA)and linear perfluorooctane sulfonate(n-PFOS),and their typical branched isomers in seawater by online solid phase extraction-liquid chromatography-tandem mass spectrometry(Online SPE-LC-MS/MS).Only centrifugation of the seawater sample was required to remove the particulate matter,and then the seawater sample was directly injected and analyzed by online SPE-LC-MS/MS.An Eclipse Plus-C18 guard column was selected as SPE column for online enrichment of linear and branched isomers,and a F5 PFP column(150 mm×2.1 mm,2.7 μm)was used as the analytical column.Under the optimized experimental conditions,the separation and detection of all PFOA and PFOS linear and branched isomers could be completed within 20 min.The spiked recoveries of various target compounds ranged from 82.9%to 107.7%with detection limits and limits of quantification of 0.10-1.05 ng/L and 0.30-2.11 ng/L,respectively.The method was characterized by good precision(RSD≤9.10%)and linearity(R2≥0.990).Subsequently,linear and branched isomers of PFOA and PFOS in surface and bottom seawater samples collected from the Laizhou Bay of China were determined.The results showed that the detection rate of all the four branched PFOA isomers were 100%,with the highest average concentration of 25.85 ng/L found for 6m-PFOA,which accounted for 11.79%of the∑PFOA.For the five branched isomers of PFOS,the highest detection rate of 90.84%was found for 5m-PFOS.The highest average concentration of 0.64 ng/L was observed for 3m-PFOS,accounting for 19.88%of ∑PFOS.The proposed method provided an effective detection tool for qualitative and quantitative detection of PFOA and PFOS isomers in the marine aquatic environment.

Objective To analyze the incidence,colonization pathways,and predictive factors of bacterial colonization of epidural analgesia catheters in patients with chronic pain.Methods A total of 150 patients with chronic pain who underwent continuous epidural catheterization(catheter in-dwelling time of 7 to 10 days)were selected as study subjects.Samples from three sites were collect-ed for bacterial culture.Clinical data of the patients were collected,and the positive rate of bacterial culture,characteristics of bacterial species distribution,and bacterial colonization pathways were ana-lyzed.The efficacy of predictive factors was assessed using the receiver operating characteristic(ROC)curve.Results The positive rates of bacterial culture in samples from the skin swabbing fluid around the puncture site,the subcutaneous segment of the catheter,and the catheter tip were 22.0％,7.3％,and 8.7％,respectively.Staphylococcus epidermidis was the predominant colonizing bacterial species.Spearman correlation coefficient analysis showed a significant correlation between the results of bacterial culture from the skin around the puncture site and catheter tip colonization(r=0.47,P＜0.01).ROC curve analysis revealed that the area under the curve of bacterial culture results from the skin around the puncture site in predicting catheter tip bacterial colonization was 0.843,with a sensitivity of 84.9％and a specificity of 84.6％.Conclusion Bacterial migra-tion along the catheter is the main pathway for catheter tip bacterial colonization,and the results of bacterial culture from the skin around the puncture site are an effective predictive factor for the risk of bacterial colonization.

Objective To investigate the effect of microglial derived extracellular vesicles on neuronal damage in the context of heat stress.Methods After BV2 microglial cells were exposed to heat stress,the supernatant was collected and subjected to ultracentrifugation at different speeds to obtain large and small vesicles,respectively.Nano Particle Tracking and Zeta Potential Distribution Analyzer was used to measure and analyze the size distribution of the large vesicles and small vesicles.Western blotting was used to detect the expression of specific vesicle surface markers,TSG101,CD63 and flotillin-1.Microglial extracellular vesicles were labeled with PKH67 dye and then co-cultured with N2a cells to examine the uptake by capacity the neurons.After large and small vesicles derived from microglia after heat stress stimulation were co-cultured with N2a cells,respectively,CCK-8 assay,lactate dehydrogenase (LDH)assay,Trypan blue staining and TUNEL assay were employed to evaluate heat stress induced neuronal damage.Results The small vesicles were in a particle size of 30～120 nm,and highly expressed TSG101 and CD63,whereas the large vesicles,in a size of 90～1000 nm,highly expressed flotillin-1.The BV2-derived extracellular vesicles could be taken up by N2a cells and were proved to be involved in the modulation of N2a cell injury caused by heat stress.CCK-8 assay showed that both large and small vesicles of microglial cells inhibited the viability of N2a cells after heat exposure (P<0.05).The results of LDH assay,Trypan blue staining and TUNEL assay showed that both large (P<0.05)and small vesicles (P<0.01)significantly enhanced the LDH release,blue stain intensity and apoptosis of N2a cells after heat exposure,and the release,intensity and apoptosis were stronger in the cells treated with small vesicles than those group of large vesicles.Conclusion Microglia aggravate heat stress-induced neuronal damage through releasing extracellular vesicles.

Objective·To investigate the biological roles and associated mechanisms of the hypoxia-induced long non-coding RNA 68(HILRNA68)in hepatocellular carcinoma(HCC)cell lines.Methods·Long non-coding RNA(lncRNA)microarray analysis was conducted to study the differential expression of lncRNAs in the HCC cell lines cultured under hypoxia treatment and normoxia treatment separately for 12 h,and DEseq2 R package was used for the analysis of differentially expressed lncRNAs.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to determine the differential lncRNAs.Short hairpin RNAs(shRNAs)were used to knock down hypoxia-inducible factors(HIFs)to investigate whether HILRNA68 transcription was regulated by HIFs under hypoxia.Nucleus-cytoplasmic isolation combined with qRT-PCR and RNA fluorescence in situ hybridization(RNA-FISH)experiments were used to investigate the subcellular localization of HILRNA68.HILRNA68 was knocked down in SMMC-7721 and MHCC-97H cells by small interfering RNA(siRNA)to investigate its cellular function under hypoxia.The impact of HILRNA68 on the cell proliferation and invasion capabilities of HCC cells under hypoxia was examined by cell counting and Transwell assays.Dual-luciferase reporter assay was employed to identify how HILRNA68 regulated the transcriptional activity of HIFs under hypoxia.Results·By differential expression analysis of lncRNAs,a total of 247 and 17 significantly(defined as fold change≥4,FDR≤0.05)up-and down-regulated IncRNAs,respectively,were identified.Among these differentially expressed genes,IncRNA HILRNA68 was up-regulated about 10-fold in multiple HCC cell lines when cultured under hypoxia for 12 h.Knockdown of HIF1α,HIF2α,and HIF1β significantly suppressed(all P＜0.05)the upregulation of HILRNA68 under hypoxia.Luciferase reporter assay suggested that the transcription of HILRNA68 was regulated by HIFs.Subcellular localization studies revealed that HILRNA68 was mainly localized in the nucleus.Biological function experiments showed that silencing of HILRNA68 significantly inhibited the proliferation and invasion of HCC cells under hypoxia(all P＜0.05).Mechanistic studies demonstrated that knock-down of HILRNA68 significantly suppressed the transcriptional activity of HIF1α under hypoxia(P＜0.05)and the up-regulation of these canonical HIFs targets under hypoxia was also significantly inhibited after HILRNA68 knockdown(P＜0.05).Conclusion·The current study identifies a series of differential hypoxia-regulated lncRNAs and functionally annotates the upregulated HILRNA68.HILRNA68 is directly up-regulated by HIFs which promotes cell proliferation and invasion under hypoxia.Mechanistically,the upregulation of HILRNA68 under hypoxia enhances the transcriptional activity of HIF1α.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.