1.WANG Qingguo's Experience in Treatment of Headache Based on the Concept of "Achieving Harmony by Unblocking and Balancing"
Chuxin ZHANG ; Zilin REN ; Yang ZHAO ; Jinhua HAN ; Bomin ZHANG ; Fafeng CHENG ; Changxiang LI ; Xueqian WANG ;
Journal of Traditional Chinese Medicine 2026;67(9):935-940
This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment", clinical presentations often involve a complex mixture of deficiency and excess, as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing", advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals, treatment should focus on dispersing and unblocking through modified Gegen Decoction (葛根汤). For wind-dampness binding, it is recommended to unblock and drain, using modified Qingshang Juantong Decoction (清上蠲痛汤). For damp-heat congestion, unblocking and clearing is the method, using modified Toufeng Shen Formula (头风神方). For liver-gallbladder qi constraint, unblocking and soothing is the treatment principle, and modified Sanpian Decoction (散偏汤) is suggested. For insufficiency of center qi, even supplementation method is recommended, and modified Yiqi Congming Decoction (益气聪明汤) can be used. For liver yang hyperactivity, unblocking and subduing are combined, using modified Xunlong Decoction (驯龙汤). For deficiency-cold in the liver and stomach, warming, harmonizing, unblocking, and descending are applied, using modified Wuzhuyu Decoction (吴茱萸汤). For blood deficiency with cold congelation, unblocking and nourishing are undertaken together, using modified Danggui Sini Decoction (当归四逆汤). The ultimate goal is to restore the dynamic balance of yin, yang, qi, and blood in the body, thereby allevia-ting pain by restoring clarity and function to the head orifices.
2.WANG Qingguo's Experience in Treatment of Headache Based on the Concept of "Achieving Harmony by Unblocking and Balancing"
Chuxin ZHANG ; Zilin REN ; Yang ZHAO ; Jinhua HAN ; Bomin ZHANG ; Fafeng CHENG ; Changxiang LI ; Xueqian WANG ;
Journal of Traditional Chinese Medicine 2026;67(9):935-940
This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment", clinical presentations often involve a complex mixture of deficiency and excess, as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing", advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals, treatment should focus on dispersing and unblocking through modified Gegen Decoction (葛根汤). For wind-dampness binding, it is recommended to unblock and drain, using modified Qingshang Juantong Decoction (清上蠲痛汤). For damp-heat congestion, unblocking and clearing is the method, using modified Toufeng Shen Formula (头风神方). For liver-gallbladder qi constraint, unblocking and soothing is the treatment principle, and modified Sanpian Decoction (散偏汤) is suggested. For insufficiency of center qi, even supplementation method is recommended, and modified Yiqi Congming Decoction (益气聪明汤) can be used. For liver yang hyperactivity, unblocking and subduing are combined, using modified Xunlong Decoction (驯龙汤). For deficiency-cold in the liver and stomach, warming, harmonizing, unblocking, and descending are applied, using modified Wuzhuyu Decoction (吴茱萸汤). For blood deficiency with cold congelation, unblocking and nourishing are undertaken together, using modified Danggui Sini Decoction (当归四逆汤). The ultimate goal is to restore the dynamic balance of yin, yang, qi, and blood in the body, thereby allevia-ting pain by restoring clarity and function to the head orifices.
3.Optical brain-computer interface: technological advances, clinical translation, and future perspectives
Ang XUAN ; Yuanjie GU ; Yiqun WANG ; Biqin DONG
Chinese Journal of Clinical Medicine 2026;33(2):193-202
Optical brain-computer interface (OBCI) represents an emerging class of neural interaction technologies that use “light” as an information carrier to enable the acquisition, decoding, and modulation of neural signals. Compared with conventional electrical brain-computer interface (BCI), OBCI demonstrates distinct advantages in spatial resolution, cell-type specificity, and the capacity for simultaneous multiparametric monitoring. Driven by rapid advances in functional near-infrared spectroscopy, optical neuroimaging, and optogenetics, optical approaches have progressively extended across the full “read, decode, write” continuum of neural activity, providing a novel technological framework for the development of high-precision closed-loop brain-computer systems. This review systematically summarizes the principal technological strategies and recent advances in OBCI, and further discusses the key challenges encountered during clinical translation, as well as future development direction.
4.Association between small vulnerable newborn phenotypes and the risk of neurodevelopmental delay at the age of 1 year: a prospective cohort study
Jinhua LU ; Songying SHEN ; Wujiangyuan HE ; Fengjuan ZHOU ; Xiaoyan XIA ; Minshan LU ; Jianrong HE ; Huimin XIA ; Xiu QIU ; Wenhao ZHOU
Chinese Journal of Pediatrics 2026;64(1):52-60
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.
5.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
6.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
7.Mechanisms of Renshentang in Treating AS via Regulation of Endothelial Cell Inflammation Based on TRPV1
Ce CHU ; Yulu YUAN ; Zhen YANG ; Xuguang TAO ; Xiangyun CHEN ; Zhanzhan HE ; Yuxin ZHANG ; Yongqi XU ; Wanping CHEN ; Peizhang ZHAO ; Wenlai WANG ; Hongxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):46-53
ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis (AS) in mice, focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 (TRPV1). MethodsAn AS model was established in apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet. The mice were randomly divided into a simvastatin group (0.02 g·kg-1·d-1) and low-, medium-, and high-dose Renshentang groups (1.77, 3.54, 7.08 g·kg-1·d-1), with 12 mice in each group. ApoE-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group (n=9). After continuous administration for 12 weeks, mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin (HE) staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), as well as the expression of TRPV1, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-Akt) in the aortic root. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect endothelial nitric oxide synthase (eNOS) mRNA expression in the aorta, and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group, the model group showed a significant increase in aortic plaque formation (P<0.01) and significantly elevated levels of TNF-α and IL-1β in the aortic root (P<0.01). The expression levels of TRPV1, p-PI3K, and p-Akt were decreased (P<0.05, P<0.01), and eNOS mRNA expression was reduced (P<0.05, P<0.01). Compared with the model group, all Renshentang groups significantly reduced aortic plaque formation (P<0.01), significantly decreased TNF-α and IL-1β levels (P<0.01), and markedly increased the expression levels of TRPV1, p-PI3K, p-Akt, and eNOS mRNA (P<0.05, P<0.01). ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway, which may be one of the molecular mechanisms underlying its therapeutic effect against AS.
8.Analysis of OCTA parameters for prognostic assessment following vitrectomy in patients with idiopathic macular epiretinal membrane
Lulu BAO ; Li WANG ; Mingliang WANG ; Min CHEN ; Zhe LIU
International Eye Science 2026;26(5):873-878
AIM: To investigate the differences in morphological structure and retinal blood perfusion between the affected eye and the contralateral healthy eye using optical coherence tomography angiography(OCTA)in patients with idiopathic macular epiretinal membrane(IMEM)before and after surgery, and to evaluate the association of these parameters with functional and anatomical outcomes to inform prognostic assessment. METHODS:A prospective study was conducted at Zhejiang Provincial People's Hospital between January 2023 and December 2024. Consecutive patients diagnosed with unilateral IMEM were enrolled; the fellow eye served as an internal control. All participants underwent standardized ophthalmic evaluations, including optical coherence tomography(OCT), OCTA, and color fundus photography. Key quantitative parameters assessed included best-corrected visual acuity(BCVA), central macular thickness(CMT), foveal avascular zone(FAZ)area, vessel density in the inner capillary plexus(ICP), superficial capillary plexus(SCP), deep capillary plexus(DCP), and choroidal capillary perfusion area(CCPA). Measurements were obtained preoperatively and at 1 and 3 mo postoperatively. Correlation analyses were performed between the above parameters and postoperative BCVA and CMT.RESULTS: This study enrolled 30 patients(60 eyes)diagnosed with IMEM, comprising 14 males and 16 females, with a mean age of 65.4±10.8 y.At baseline, IMEM-affected eyes demonstrated significantly reduced BCVA, DCP density, and FAZ area, alongside significantly increased CMT and CCPA, compared with contralateral controls. Following vitrectomy with membrane peeling, CMT decreased significantly at both 1 and 3 mo(both P<0.05)postoperatively; DCP density and BCVA showed significant improvement(both P<0.05). No significant change in FAZ area was observed postoperatively(P>0.05). At 3 mo postoperatively, BCVA of the affected eye was negatively correlated with CMT(r=-0.549, P=0.022). At 1 mo postoperatively, CMT was negatively correlated with preoperative DCP and FAZ, positively correlated with preoperative CMT, and positively correlated with ICP and SCP at 1 mo postoperatively, and negatively correlated with FAZ at 1 mo postoperatively(all P<0.05). Furthermore, CMT at 3 mo postoperatively was negatively correlated with preoperative DCP(r=-0.498,P=0.042).CONCLUSION:In patients with IMEM, the affected eyes exhibit significantly reduced DCP density and FAZ area, alongside increased CMT and CCPA. Following vitrectomy with membrane peeling, CMT decreased progressively, DCP density demonstrated partial restoration, and vision improved gradually. Preoperatively, smaller CMT larger DCP, and FAZ were associated with more favorable surgical outcomes; postoperatively, smaller ICP and SCP densities—combined with a larger FAZ—also correlated with better functional recovery.
9.Mechanisms of Huanglian Jiedutang and Its Major Active Constituents in Inhibiting LPS-induced M1 Polarisation of BV2 Microglia
Haojia ZHANG ; Kai WANG ; Kunjing LIU ; Xin LAN ; Zijin SUN ; Chunyu WANG ; Wenyuan MA ; Wei SHAO ; Jinhua HAN ; Liyang DONG ; Changxiang LI ; Xueqian WANG ; Youxiang CUI ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):44-55
ObjectiveTo investigate whether Huanglian Jiedutang (HLJD) and its major active constituents (geniposide, baicalin, and berberine) can inhibit the inflammatory response of BV2 cells under lipopolysaccharide (LPS) stimulation via the high-mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, and to explore differences in therapeutic efficacy among the three monomers, their combined formula, and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 (CCK-8) method to examine the effects of different concentrations of dimethyl sulfoxide (DMSO, 0.8%, 0.4%, 0.2%, 0.1%, and 0.05%) on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD (200, 100, 50, 25, 12.5, 6.25 mg·L-1). Nitric oxide (NO) assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography (HPLC) determined the content of geniposide, baicalin, and berberine in HLJD, and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay (ELISA) measured levels of inflammatory factors (TNF-α, IL-1β, IL-6, IL-10) in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1, TLR4, and NF-κB-related proteins. ResultsCompared with the blank group, DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L-1 HLJD. Under stimulation with 2 mg·L-1 LPS, this concentration of HLJD effectively reduced NO release, and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide, 15 μg of baicalin, and 30 μg of berberine. Based on these ratios, experimental groups were blank, LPS (2 mg·L-1), HLJD (200 mg·L-1), monomer combination, geniposide (4.8 mg·L-1), baicalin (3 mg·L-1), and berberine (6 mg·L-1). The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α, IL-1β, IL-6, and IL-10 in the supernatant (P<0.01). HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01) while upregulating anti-inflammatory IL-10 (P<0.01), with the monomer combination showing the strongest effect (P<0.05, P<0.01). Compared with the blank group, LPS significantly increased the proportion of CD80⁺CD86⁺ (M1-type) BV2 cells (P<0.01). HLJD and its constituents partially inhibited M1 polarization (P<0.05, P<0.01), with the monomer combination exhibiting the most pronounced effect (P<0.05, P<0.01). Compared with the blank group, LPS upregulated HMGB1, TLR4, and NF-κB-related proteins (P<0.01), whereas HLJD and its active constituents significantly reduced their expression (P<0.05, P<0.01), with the monomer combination having the strongest regulatory effect (P<0.05, P<0.01). ConclusionHLJD and its major active constituents (geniposide, baicalin, berberine) can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect, significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.
10.Association between small vulnerable newborn phenotypes and the risk of neurodevelopmental delay at the age of 1 year: a prospective cohort study
Jinhua LU ; Songying SHEN ; Wujiangyuan HE ; Fengjuan ZHOU ; Xiaoyan XIA ; Minshan LU ; Jianrong HE ; Huimin XIA ; Xiu QIU ; Wenhao ZHOU
Chinese Journal of Pediatrics 2026;64(1):52-60
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.

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