Digital and intelligent technologies serve as the core engine driving the inheritance of the essence and the innovation while upholding the fundamentals of traditional Chinese medicine（TCM）. Currently， the digital and intelligent transformation of TCM has undergone four developmental stages， exhibiting inherent characteristics such as long-term inevitability， objective standardization， and ecological evolution. By introducing quantitative metrics， digital and intelligent technologies have achieved breakthroughs in TCM knowledge inheritance and innovation， clinical diagnosis and treatment， and herbal medicine supply. The practical applicability of methodological innovations has been empirically validated， though significant disparities exist in technological adaptability and application depth across different fields. Overall， the digital and intelligent transformation of TCM remains in its nascent stage， grappling with multiple structural challenges：weak data foundations， inadequate technological adaptability， incomplete institutional frameworks， shortages of multidisciplinary talent， lagging policies and regulations， and urban-rural digital divide. In order to foster sustainable development and modernization of TCM， this paper establishes a six-dimensional collaborative governance framework of encompassing data， technology， organization， institutions， environment and ethics， which is rooted in data governance and digital governance theories. Future efforts should center on standardization， integration， and ecosystem development to build a data and technology foundation. Focus should be placed on deepening innovation and application of key TCM-specific technologies， while simultaneously strengthening interdisciplinary talent cultivation， improving institutional mechanisms and policy frameworks， and increasing support for rural areas. By adopting a people-centered and technology-empowered approach， we can overcome developmental constraints and unleash the powerful driving force of digital and intelligent technologies for the inheritance of TCM.

Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Sleep fragmentation， characterized by disrupted nocturnal sleep，is a core manifestation of chronic insomnia and exhibits a close and complex bidirectional relationship with Alzheimer disease （AD）. On the one hand， sleep fragmentation impairs glymphatic system function， reducing the clearance efficiency of toxic metabolites such as amyloid-beta （Aβ） and tau proteins in the brain interstitial fluid， thereby acting as a promoting factor for AD. Concurrently， sleep disturbances directly dysregulate pathogenic protein dynamics，and chronic sleep deprivation exacerbates neuroinflammation and oxidative stress， worsening the AD pathological environment.On the other hand， inherent AD pathological changes further aggravate sleep fragmentation. Damage to brain regions associated with AD leads to circadian rhythm disruption and reduced non-rapid eye movement （NREM） sleep.Additionally，imbalances in neurotransmitters such as orexin and melatonin during AD progression contribute to the disintegration of the sleep-wake cycle. This review aims to explore the mutual interactions between sleep fragmentation and AD， identify current research gaps， and provide new directions for future studies.

Objective　To evaluate the in vitro synergistic antimicrobial effect of allicin combined with imipenem on clinically isolated carbapenem-resistant Klebsiella pneumoniae (CRKP), providing a reference for further in vivo pharmacodynamic studies. Methods Twenty-two strains of CRKP were selected as experimental subjects based on clinical drug sensitivity results. Pulling assay together with carbapenem inhibition enhancement assay were leveraged to identify the high adherence and β-lactamase phenotypes of CRKP. The combined effect of allicin and imipenem was confirmed using the zero interaction potency (ZIP) method. The antimicrobial effects of allicin, imipenem, and their combination against CRKP were tested separately in vitro by agar paper diffusion method. The organic combination of allicin and imipenem was exploited for detecting the diameter of the CRKP inhibitory circle and minimal inhibitory concentration (MIC). The crystal violet semi-quantitative method was utilized to observe the effect of allicin combined with imipenem on CRKP biofilm formation. Results Among the 22 strains of CRKP, 6 strains exhibited high adhesion, accounting for 27.27%. The results of carbapenem inhibition enhancement demonstrated that all strains of CRKP were class A β-lactamase-producing. Allicin had a strong bactericidal effect on CRKP. According to the results of one-way ANOVA, the diameter of the circle of inhibition of allicin combined with imipenem (15.91±2.76)mm was significantly higher than that of the imipenem alone group (8.23±3.46) mm(F=46.39, P<0.001). The ZIP scoring and MIC methods confirmed that the combination of allicin and imipenem primarily exerted an additive effect. One-way ANOVA analysis of crystal violet absorbance values showed that compared to the control group (0.213±0.056), the total CRKP biofilm amount in the allicin combined with imipenem group was reduced (0.134±0.045) (F=3.211, P=0.045). Conclusions The results of bacterial inhibition experiments in vitro show that the combination of allicin and imipenem significantly increases the inhibitory ability of CRKP and inhibits biofilm formation effectively.

Objective:To investigate the efficacy and influencing factors of iodine-125 seed implantation in the treatment of recurrent radioiodine refractory differentiated thyroid carcinoma (RAIR-DTC) .Methods:Retrospective analysis of 18 patients with recurrent RAIR-DTC treated with iodine-125 particle implantation at Ward One, Department of Oncology, Hebei General Hospital from Sept. 2015 to Mar. 2022 was performed. A total of 35 lesions were involved, all permanently implanted with iodine-125 particles under image guidance, with particle activity ranging from 0.3mCi to 0.8mCi, and prescription doses ranging from 80 to 140 Gy. The study observed the objective response rate, local control rate, survival rate, adverse reactions, and factors influencing treatment efficacy.Results:After a follow-up period of 8 to 115 months,according to the objective efficacy evaluation criteria of solid tumors 1.1,the objective response rates were 51.4% (18/35) ,80.0% (28/35) ,68.6% (24/35) ,60.0% (21/35) ,42.9% (15/35) at 3,6,12,24,36 months postoperatively,respectively.The local control rates were 100% (35/35) ,100% (35/35) ,80.0% (28/35) ,62.9% (22/35) ,51.4% (18/35) at 3,6,12,24,36 months postoperatively,respectively.The 1-,2-, and 3-year postoperative survival rates were 83.3% (15/18) ,72.2% (13/18) ,61.1% (11/18) ,respectively.During the follow-up period,4 patients developed progressive lesions in the target area.One grade I radioactive skin injury,one grade Ⅱ radioactive skin injury,and no residual particle-related adverse reactions.The results of multivariate analysis showed that D90,tumor involvement of the esophagus were the factors influencing the recent efficacy.The area under the ROC curve for D90 was 0.804 with the best bound of 106.5Gy.Conclusion:Iodine-125 particle implantation is safe and effective for recurrent RAIR-DTC.D90,tumor involvement of the esophagus are the influencing factors of the recent efficacy,and the D90≥106.5Gy treatment effect is better.

Objective:To describe the current status and changes of multisymptom burden during the post-transplant hematopoietic reconstruction period in children with hematopoietic stem cell transplantation, and to provide reference for the precise management of symptoms in post-transplantation children.Methods:Children aged 7-18 years who underwent hematopoietic stem cell transplantation in Shanghai Children′s Medical Centre, Shanghai Jiao Tong University School of Medicine from September 2022 to October 2023 were selected by convenience sampling method. The Pediatric Patient Reported Outcomes version of Common Terminology Criteria for Adverse Events was used to assess multiple symptoms and burden during the reconstruction period on days 0, 7, 14, and 21 after transplantation.Results:Finally, 90 children who underwent hematopoietic stem cell transplantation were investigated, including 61 males and 29 females, aged (9.98 ± 2.96) years old. On days 0, 7, 14, and 21 after transplantation, the number of symptoms, severity of symptoms, degree of symptom interference were 20.00 (14.00), 18.00 (14.50), and 10.00 (9.75), with scores of 0.18 (0.30), 0.14 (0.29), 0.08 (0.13), 0.00 (0.08), and 0.27 (0.42), 0.19 (0.30), 0.09 (0.16), 0.03 (0.11), respectively. The overall differences were statistically significant ( Z=101.69, 93.70, 96.65, all P<0.01). The symptom burden in children showed four different trajectories including higher symptom burden in the early stages and lower in the later stages, consistently high burden, high symptom burden followed by low symptom burden, and consistently low burden. Conclusions:Children after hematopoietic stem cell transplantation are plagued by multiple symptoms during hematopoietic reconstruction, and with the treatment and time, different symptoms show different trajectories of change. Healthcare professionals should accurately assess the symptomatic changes of children after transplantation and provide targeted interventions to reduce the symptomatic burden and promote the recovery of children.

Objective:To investigate the efficacy and influencing factors of iodine-125 seed implantation in the treatment of recurrent radioiodine refractory differentiated thyroid carcinoma (RAIR-DTC) .Methods:Retrospective analysis of 18 patients with recurrent RAIR-DTC treated with iodine-125 particle implantation at Ward One, Department of Oncology, Hebei General Hospital from Sept. 2015 to Mar. 2022 was performed. A total of 35 lesions were involved, all permanently implanted with iodine-125 particles under image guidance, with particle activity ranging from 0.3mCi to 0.8mCi, and prescription doses ranging from 80 to 140 Gy. The study observed the objective response rate, local control rate, survival rate, adverse reactions, and factors influencing treatment efficacy.Results:After a follow-up period of 8 to 115 months,according to the objective efficacy evaluation criteria of solid tumors 1.1,the objective response rates were 51.4% (18/35) ,80.0% (28/35) ,68.6% (24/35) ,60.0% (21/35) ,42.9% (15/35) at 3,6,12,24,36 months postoperatively,respectively.The local control rates were 100% (35/35) ,100% (35/35) ,80.0% (28/35) ,62.9% (22/35) ,51.4% (18/35) at 3,6,12,24,36 months postoperatively,respectively.The 1-,2-, and 3-year postoperative survival rates were 83.3% (15/18) ,72.2% (13/18) ,61.1% (11/18) ,respectively.During the follow-up period,4 patients developed progressive lesions in the target area.One grade I radioactive skin injury,one grade Ⅱ radioactive skin injury,and no residual particle-related adverse reactions.The results of multivariate analysis showed that D90,tumor involvement of the esophagus were the factors influencing the recent efficacy.The area under the ROC curve for D90 was 0.804 with the best bound of 106.5Gy.Conclusion:Iodine-125 particle implantation is safe and effective for recurrent RAIR-DTC.D90,tumor involvement of the esophagus are the influencing factors of the recent efficacy,and the D90≥106.5Gy treatment effect is better.

OBJECTIVE To explore the clinical characteristics of Tropheryma whipplei(TW)infection and observe the application of pathogenic metagenomic next-generation sequencing(mNGS)in diagnosis of TW infection.METHODS The clinical data were collected from 1 patient who was diagnosed by mNGS in the Affiliated Hospital of Jining Medical University on Apr.9,2022.The data including the results of laboratory tests and treatment out-comes were summarized,and a literature review was conducted.RESULTS A 50-year-old woman presented to the hospital with chest tightness and chest pain lasting for 3 days,accompanied by dyspnea,palpitations,and expec-toration.The chest plain CT scan and magnetic resonance imaging(MRI)scan suggested a high probability of pul-monary infection.Normal flora were isolated by culture of bronchoalveolar lavage fluid(BALF);TW and human βherpes virus type 7 were detected in BALF by mNGS,with the sequence numbers 327 000 and 9,respectively.The pulmonary symptoms of the patient were improved after joint treatment of the infection with etimicin,levo-floxacin and minocycline.The patient repeatedly sought for medical treatment due to the pain of shoulder joint and limitation of motion.CONCLUSIONS TW is one of major pathogens leading to the infections of systemic multiple systems,and it is necessary to attach great importance to the diagnosis and treatment.The traditional laboratory test method can not achieve ideal diagnosis effect and is more likely to make a missed diagnosis.mNGS is more ac-curate and more efficient than the traditional detection method in diagnosis of TW-induced diseases.Early use of mNGS can make a rapid identification of pathogens and facilitate the reasonable clinical use of antibiotics.It is of great significance for control of the disease progression,improvement of prognosis and prevention of recurrence.

OBJECTIVE To explore the clinical characteristics of Tropheryma whipplei(TW)infection and observe the application of pathogenic metagenomic next-generation sequencing(mNGS)in diagnosis of TW infection.METHODS The clinical data were collected from 1 patient who was diagnosed by mNGS in the Affiliated Hospital of Jining Medical University on Apr.9,2022.The data including the results of laboratory tests and treatment out-comes were summarized,and a literature review was conducted.RESULTS A 50-year-old woman presented to the hospital with chest tightness and chest pain lasting for 3 days,accompanied by dyspnea,palpitations,and expec-toration.The chest plain CT scan and magnetic resonance imaging(MRI)scan suggested a high probability of pul-monary infection.Normal flora were isolated by culture of bronchoalveolar lavage fluid(BALF);TW and human βherpes virus type 7 were detected in BALF by mNGS,with the sequence numbers 327 000 and 9,respectively.The pulmonary symptoms of the patient were improved after joint treatment of the infection with etimicin,levo-floxacin and minocycline.The patient repeatedly sought for medical treatment due to the pain of shoulder joint and limitation of motion.CONCLUSIONS TW is one of major pathogens leading to the infections of systemic multiple systems,and it is necessary to attach great importance to the diagnosis and treatment.The traditional laboratory test method can not achieve ideal diagnosis effect and is more likely to make a missed diagnosis.mNGS is more ac-curate and more efficient than the traditional detection method in diagnosis of TW-induced diseases.Early use of mNGS can make a rapid identification of pathogens and facilitate the reasonable clinical use of antibiotics.It is of great significance for control of the disease progression,improvement of prognosis and prevention of recurrence.