Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma.

BACKGROUND: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. METHODS: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. FINDINGS: 89Zr/177Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. INTERPRETATION: 89Zr- and 177Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Loss of opioid binding protein/cell adhesion molecule-like gene expression in gastric cancer.

Previous studies have reported that the expression of the opioid binding protein/cell adhesion molecule-like (OPCML) gene was frequently downregulated in various of types of cancer. However, little is known regarding the expression of the OPCML gene in gastric cancer. The present study identified that OPCML was downregulated in the gastric cancer SGC7901, KATO III, MKN45, MKN74, SNU1, AGS, N87 and a gastric mucosa cell line GES1, compared with normal gastric tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To investigate whether the downregulation of OPCML was due to promoter hypermethylation, the methylation of the OPCML promoter was assessed by methylation-specific polymerase chain reaction. Hypermethylation of the OPCML promoter was observed in the gastric cancer MKN45 cell lines, but was not as evident in normal gastric tissue. The methylation inhibitor 5-aza-2'-deoxycytidine was used to remove the methylation of the OPCML gene promoter, following which the expression of OPCML was restored. In addition, the function of the OPCML gene was studied in vitro, and it was found that the restoration expression of OPCML could lead to the suppression of cell growth. In conclusion, the present study has shown that OPCML, which acts as a tumor suppressor, was silenced in gastric cancer cell lines via aberrant hypermethylation of the promoter CpG islands, which may provide a novel molecular approach for the early diagnosis of gastric cancer.

Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

Effects of Ligand Geometry on the Photophysical Properties of Photoluminescent Eu(III) and Sm(III) 1-Hydroxypyridin-2-one Complexes in Aqueous Solution.

A series of 10 tetradentate 1-hydroxy-pyridin-2-one (1,2-HOPO) ligands and corresponding eight-coordinated photoluminescent Eu(III) and Sm(III) complexes were prepared. Generally, the ligands differ by the linear (nLI) aliphatic linker length, from 2 to 8 methylene units between the bidentate 1,2-HOPO chelator units. The photoluminescent quantum yields (Φtot) were found to vary with the linker length, and the same trend was observed for the Eu(III) and Sm(III) complexes. The 2LI and 5LI bridged complexes are the brightest (Φtotxε). The change in ligand wrapping pattern between 2LI and 5LI complexes observed by X-ray diffraction (XRD) is further supported by density functional theory (DFT) calculations. The bimodal Φtot trends of the Eu(III) and Sm(III) complexes are rationalized by the change in ligand wrapping pattern as the bridge (nLI) is increased in length.

Calcitriol prevents peripheral RSC96 Schwann neural cells from high glucose & methylglyoxal-induced injury through restoration of CBS/H2S expression.

A meta-analysis has suggested that vitamin D deficiency is involved in diabetic peripheral neuropathy (DPN) and the levels of hydrogen sulfide (H2S) are also decreased in type 2 diabetes. The injection of vitamin D induces cystathionine-ß-synthase (CBS) expression and H2S generation. However, it remains unclear whether the supplementation of vitamin D prevents DPN through improvement of CBS/H2S expression. In the present study, RSC96 cells, a rat Schwann cell line, were exposed to high glucose and methylglyoxal (HG&MG) to simulate diabetic peripheral nerve injury in vivo. Before the exposure to HG&MG, the cells were preconditioned with calcitriol (CCT), an active form of vitamin D, and then CCT-mediated neuroprotection was investigated in respect of cellular viability, superoxide anion (O2(-)) generation, inducible nitric oxide (NO) synthase (iNOS)/NO expression, mitochondrial membrane potential (MMP), as well as CBS expression and activity. It was found that both high glucose and MGO decreased cell viability and co-treatment with the two induced a more serious injury in RSC96 cells. Therefore, the exposure to HG&MG was used in the present study. The exposure to HG&MG markedly induced iNOS expression, NO and O2(-) generation, as well as MMP loss. In addition, the exposure to HG&MG depressed CBS expression and activity in RSC96 cells. However, the preconditioning with CCT significantly antagonized HG&MG-induced cell injury including the decreased viability, iNOS overexpression, NO and O2(-) accumulation, as well as MMP loss. CCT also partially restored the decreased CBS expression and activity triggered by HG&MG, while the inhibition of CBS with hydroxylamine attenuated CCT-mediated neuroprotection. Moreover, the exogenous donation of H2S produced similar cellular protective effects to CCT. The data indicate that the supplementation of vitamin D prevents HG&MG-induced peripheral nerve injury involving the restoration of endogenous H2S system, which may provide a basal support for the treatment of DPN with vitamin D clinically.

Optimization of the Sensitization Process and Stability of Octadentate Eu(III) 1,2-HOPO Complexes.

The synthesis of a series of octadentate ligands containing the 1-hydroxypyridin-2-one (1,2-HOPO) group in complex with europium(III) is reported. Within this series, the central bridge connecting two diethylenetriamine units linked to two 1,2-HOPO chromophores at the extremities (5-LIN-1,2-HOPO) is varied from a short ethylene chain (H(2,2)-1,2-HOPO) to a long pentaethylene oxide chain (H(17O5,2)-1,2-HOPO). The thermodynamic stability of the europium complexes has been studied and reveals these complexes may be effective for biological measurements. Extension of the central bridge results in exclusion of the inner-sphere water molecule observed for [Eu(H(2,2)-1,2-HOPO)](-) going from a nonacoordinated to an octacoordinated Eu(III) ion. With the longer chain length ligands, the complexes display increased luminescence properties in aqueous medium with an optimum of 20% luminescence quantum yield for the [Eu(H(17O5,2)-1,2-HOPO)](-) complex. The luminescence properties for [Eu(H(14O4,2)-1,2-HOPO)](-) and [Eu(H(17O5,2)-1,2-HOPO)](-) are better than that of the model bis-tetradentate [Eu(5LIN(Me)-1,2-HOPO)2](-) complex, suggesting a different geometry around the metal center despite the geometric freedom allowed by the longer central chain in the H(mOn,2) scaffold. These differences are also evidenced by examining the luminescence spectra at room temperature and at 77 K and by calculating the luminescence kinetic parameters of the europium complexes.

A novel controllable hydrogen sulfide-releasing molecule protects human skin keratinocytes against methylglyoxal-induced injury and dysfunction.

BACKGROUND/AIM: Delayed wound healing is a common skin complication of diabetes, which is associated with keratinocyte injury and dysfunction. Levels of methylglyoxal (MGO), an α-dicarbonyl compound, are elevated in diabetic skin tissue and plasma, while levels of hydrogen sulfide (H2S), a critical gaseous signaling molecule, are reduced. Interestingly, the gas has shown dermal protection in our previous study. To date, there is no evidence demonstrating whether MGO affects keratinocyte viability and function or H2S donation abolishes these effects and improves MGO-related impairment of wound healing. The current study was conducted to examine the effects of MGO on the injury and function in human skin keratinocytes and then to evaluate the protective action of a novel H2S-releasing molecule. METHODS: An N-mercapto-based H2S donor (NSHD)-1 was synthesized and its ability to release H2S was observed in cell medium and cells, respectively. HaCaT cells, a cell line of human skin keratinocyte, were exposed to MGO to establish an in vitro diabetic wound healing model. NSHD-1 was added to the cells before MGO exposure and the improvement of cell function was observed in respect of cellular viability, apoptosis, oxidative stress, mitochondrial membrane potential (MMP) and behavioral function. RESULTS: Treatment with MGO decreased cell viability, induced cellular apoptosis, increased intracellular reactive oxygen species (ROS) content and depressed MMP in HaCaT cells. The treatment also damaged cell behavioral function, characterized by decreased cellular adhesion and migration. The synthesized H2S-releasing molecule, NSHD-1, was able to increase H2S levels in both cell medium and cells. Importantly, pretreatment with NSHD-1 inhibited MGO-induced decreases in cell viability and MMP, increases in apoptosis and ROS accumulation in HaCaT cells. The pretreatment was also able to improve adhesion and migration function. CONCLUSION: These results demonstrate that the novel synthesized H2S donor is able to protect human skin keratinocytes against MGO-induced injury and behavior dysfunction. We believe that more reasonable H2S-releasing molecules will bring relief to patients suffering from delayed wound healing in diabetes mellitus in the future.

A macrocyclic chelator with unprecedented Th4⁺ affinity.

A novel macrocyclic octadentate ligand incorporating terephthalamide binding units has been synthesized and evaluated for the chelation of Th(4+). The thorium complex was structurally characterized by X-ray diffraction and in solution with kinetic studies and spectrophotometric titrations. Dye displacement kinetic studies show that the ligand is a much more rapid chelator of Th(4+) than prevailing ligands (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and diethylenetriaminepentaacetic acid). Furthermore, the resulting complex was found to have a remarkably high thermodynamic stability, with a formation constant of 10(54). These data support potential radiotherapeutic applications.

Curcumin inhibits the proliferation of airway smooth muscle cells in vitro and in vivo.

The inhibition of the proliferation of airway smooth muscle cells (ASMCs) is crucial for the prevention and treatment of asthma. Recent studies have revealed some important functions of curcumin; however, its effects on the proliferation of ASMCs in asthma remain unknown. Therefore, in this study, we performed in vitro and in vivo experiments to investigate the effects of curcumin on the proliferation of ASMCs in asthma. The thickness of the airway wall, the airway smooth muscle layer, the number of ASMCs and the expression of extracellular signal-regulated kinase (ERK) were significantly reduced in the curcumin-treated group as compared with the model group. Curcumin inhibited the cell proliferation induced by platelet-derived growth factor (PDGF) and decreased the PDGF-induced phosphorylation of ERK1/2 in the rat ASMCs. Moreover, the disruption of caveolae using methyl-ß-cyclodextrin (MßCD) attenuated the anti-proliferative effects of curcumin in the ASMCs, which suggests that caveolin is involved in this process. Curcumin upregulated the mRNA and protein expression of caveolin-1. The data presented in this study demonstrate that the proliferation of ASMCs is inhibited by curcumin in vitro and in vivo; curcumin exerts these effects by upregulating the expression of caveolin-1 and blocking the activation of the ERK pathway.

Campylobacter jejuni ferric-enterobactin receptor CfrA is TonB3 dependent and mediates iron acquisition from structurally different catechol siderophores.

Campylobacter jejuni NCTC11168 does not produce any endogenous siderophores of its own yet requires the CfrA enterobactin transporter for in vivo colonization. In addition, the genome of C. jejuni NCTC11168 contains three distinct TonB energy transduction systems, named TonB1, TonB2, and TonB3, that have not been tested for their role in siderophore uptake or their functional redundancy. We demonstrate that C. jejuni NCTC11168 transports ferric-enterobactin in an energy dependent manner that requires TonB3 for full activity with TonB1 showing partial functional redundancy. Moreover C. jejuni NCTC11168 can utilize a wide variety of structurally different catechol siderophores as sole iron sources during growth. This growth is solely dependent on the CfrA enterobactin transporter and highlights the wide range of substrates that this transporter can recognize. TonB3 is also required for growth on most catechol siderophores. Furthermore, either TonB1 or TonB3 is sufficient for growth on hemin or hemoglobin as a sole iron source demonstrating functional redundancy between TonB1 and TonB3. In vivo colonization assays with isogenic deletion mutants revealed that both TonB1 and TonB3 are required for chick colonization with TonB2 dispensable in this model. These results further highlight the importance of iron transport for efficient C. jejuni colonization.

Circularly polarized luminescence of curium: a new characterization of the 5f actinide complexes.

A key distinction between the lanthanide (4f) and the actinide (5f) transition elements is the increased role of f-orbital covalent bonding in the latter. Circularly polarized luminescence (CPL) is an uncommon but powerful spectroscopy which probes the electronic structure of chiral, luminescent complexes or molecules. While there are many examples of CPL spectra for the lanthanides, this report is the first for an actinide. Two chiral, octadentate chelating ligands based on orthoamide phenol (IAM) were used to complex curium(III). While the radioactivity kept the amount of material limited to micromole amounts, spectra of the highly luminescent complexes showed significant emission peak shifts between the different complexes, consistent with ligand field effects previously observed in luminescence spectra.

Structural and photophysical properties of visible- and near-IR-emitting tris lanthanide(III) complexes formed with the enantiomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide.

The enantiomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide (L), namely, (R,R)-1, and (S,S)-1, react with Ln(III) ions to give stable [LnL(3)](3+) complexes in an anhydrous acetonitrile solution and in the solid state, as evidenced by electrospray ionization mass spectrometry, NMR, luminescence titrations, and their X-ray crystal structures, respectively. All [LnL(3)](3+) complexes [Ln(III) = Eu, Gd, Tb, and Yb; L = (R,R)-1 and (S,S)-1] are isostructural and crystallize in the cubic space group I23. Although the small quantum yields of the Ln(III)-centered luminescence clearly point to the poor efficiency of the luminescence sensitization by the ligand and the intersystem crossing and ligand-to-metal energy transfers, the ligand triplet-excited-state energy seems relatively well suited to sensitize many Ln(III) ion's emission for instance, in the visible (Eu and Tb), near-IR (Nd and Yb), or both regions (Pr, Sm, Dy, Er, and Tm).

Octadentate cages of Tb(III) 2-hydroxyisophthalamides: a new standard for luminescent lanthanide labels.

The synthesis, structure, and photophysical properties of several Tb(III) complexes with octadentate, macrotricyclic ligands that feature a bicapped topology and 2-hydroxyisophthalamide (IAM) chelating units are reported. These Tb(III) complexes exhibit highly efficient emission (Φ(total) ≥ 50%), large extinction coefficients (ε(max) ≥ 20,000 M(-1) cm(-1)), and long luminescence lifetimes (τ(H(2)O) ≥ 2.45 ms) at dilute concentrations in standard biological buffers. The structure of the methyl-protected ligand was determined by single-crystal X-ray diffraction and confirms the macrotricyclic structure of the parent ligand; the amide groups of the methyl-protected cage compound generate an anion binding cavity that complexes a chloride anion. Once the ligand is deprotected, a conformational change generates a similar cavity, formed by the phenolate and ortho amide oxygen groups that strongly bind lanthanide ions. The Tb(III) complexes thus formed display long-term stability, with little if any change in their spectral properties (including lifetime, quantum yield, and emission spectrum) over time or in different chemical environments. Procedures to prepare functionalized derivatives with terminal amine, carboxylate, and N-hydroxysuccinimide groups suitable for derivatization and protein bioconjugation have also been developed. These bifunctional ligands have been covalently attached to a number of different proteins, and the terbium complexes' exceptional photophysical properties are retained. These compounds establish a new aqueous stability and quantum yield standard for long-lifetime lanthanide reporters.

Eu(III) complexes of functionalized octadentate 1-hydroxypyridin-2-ones: stability, bioconjugation, and luminescence resonance energy transfer studies.

The synthesis, stability, and photophysical properties of several Eu(III) complexes featuring the 1-hydroxypyridin-2-one (1,2-HOPO) chelate group in tetradentate and octadentate ligands are reported. These complexes pair highly efficient emission with exceptional stabilities (pEu ∼ 20.7-21.8) in aqueous solution at pH 7.4. Further analysis of their solution behavior has shown the observed luminescence intensity is significantly diminished below about pH ∼ 6 because of an apparent quenching mechanism involving protonation of the amine backbones. Nonetheless, under biologically relevant conditions, these complexes are promising candidates for applications in Homogeneous Time-Resolved Fluorescence (HTRF) assays and synthetic methodology to prepare derivatives with either a terminal amine or a carboxylate group suitable for bioconjugation has been developed. Lastly, we have demonstrated the use of these compounds as the energy donor in a Luminescence Resonance Energy Transfer (LRET) biological assay format.

Biomimetic actinide chelators: an update on the preclinical development of the orally active hydroxypyridonate decorporation agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO).

The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity, and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (>100 micromol kg d) over 28 d under good laboratory practice guidelines. Both compounds are on an accelerated development pathway towards clinical use.

1-Methyl-3-hydroxy-pyridin-2-one complexes of near infra-red emitting lanthanides: efficient sensitization of Yb(III) and Nd(III) in aqueous solution.

The synthesis, X-ray structure, solution stability, and photophysical properties of several trivalent lanthanide complexes of Yb(III) and Nd(III) using both tetradentate and octadentate ligand design strategies and incorporating the 1-methyl-3-hydroxy-pyridin-2-one (Me-3,2-HOPO) chelate group are reported. Both the Yb(III) and Nd(III) complexes have emission bands in the Near Infra-Red (NIR) region, and this luminescence is retained in aqueous solution (Phi(tot)(Yb) approximately 0.09-0.22%).Furthermore, the complexes demonstrate very high stability (pYb approximately 18.8-21.9) in aqueous solution, making them good candidates for further development as probes for NIR imaging. Analysis of the low temperature (77 K) photophysical measurements for a model Gd(III) complex were used to gain an insight into the electronic structure, and were found to agree well with corresponding time-dependent density functional theory (TD-DFT) calculations at the B3LYP/6-311G++(d,p) level of theory for a simplified model monovalent sodium complex.

Novel sorbents for removal of gadolinium-based contrast agents in sorbent dialysis and hemoperfusion: preventive approaches to nephrogenic systemic fibrosis.

Many forms of organocomplexed gadolinium (Gd) contrast agents have recently been linked to a debilitating and a potentially fatal skin disease called nephrogenic systemic fibrosis (NSF) in patients with renal failure. Free Gd released from these complexes via transmetallation is believed to be the most important trigger for NSF. In this work, nanostructure silica materials that have been functionalized with 1-hydroxy-2-pyridinone (1,2-HOPO-SAMMS) have been evaluated for selective and effective removal of both free and chelated Gd (gadopentetate dimeglumine and gadodiamide) from dialysate and blood. 1,2-HOPO SAMMS has high affinity, rapid removal rate, and large sorption capacity for both free and chelated Gd, properties that are far superior to those of activated carbon and zirconium phosphate currently used in the state-of-the-art sorbent dialysis and hemoperfusion systems. The SAMMS-based sorbent dialysis and hemoperfusion will potentially provide an effective and predicable strategy for removing the Gd from patients with impaired renal function after Gd exposure, thus allowing for the continued use of Gd-based contrast magnetic resonance imaging while removing the risk of NSF. FROM THE CLINICAL EDITOR: Chelated gadolinium (Gd) contrast agents have been linked to a debilitating disease called nephrogenic systemic fibrosis (NSF) in patients with renal failure. Free Gd+(3) released from the contrast agents is believed to be the trigger for NSF. In this work, functionalized nanostructured silica materials were evaluated for removal of both free and chelated gadolinium both from dialysate and blood. The new method demonstrated a rapid removal rate and large sorption capacity, and overall was far superior to currently used state-of-the-art sorbent dialysis and hemoperfusion systems.

Aryl bridged 1-hydroxypyridin-2-one: effect of the bridge on the Eu(III) sensitization process.

The efficiency of Eu(3+) luminescence by energy transfer from an antenna ligand can be strongly dependent on the metal ion coordination geometry. The geometric component of the Eu(III) sensitization has been probed using series of tetradentate 1,2-HOPO derivatives that are connected by bridges of varying length and geometry. The ligands are N,N'-(1,2-phenylene)bis(1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamide) for the ligand (L(1)), 1-hydroxy-N-(2-(1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamido)benzyl)-6-oxo-1,6-dihydropyridine-2-carboxamide (L(2)) and N,N'-(1,2-phenylenebis(methylene))bis(1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamide) (L(3)). Spectroscopic characterization of both the Gd(III) and the Eu(III) metal complexes, time-dependent density functional theory (TD-DFT) analysis of model compounds and evaluation of the kinetic parameters for the europium emission were completed. Some striking differences were observed in the luminescence quantum yield by altering the bridging unit. The [Eu(L(2))(2)](-) derivative shows efficient sensitization coupled with good metal centered emission. For [Eu(L(3))(2)](-), the large quenching of the luminescence quantum yield compared to [Eu(L(2))(2)](-) is primarily a result of one inner sphere water molecule bound to the europium cation while for [Eu(L(1))(2)](-), the low luminescence quantum yield can be attributed to inefficient sensitization of the europium ion.

[Key parameters and formulas for approximate average height and weight of normal Chinese children under 7 years of age].

OBJECTIVE: In order to understand the normal physical growth of Chinese children, data of children aged from 0 to 7 years from urban and rural areas of nine Chinese cities in 2005 were analyzed. METHODS: The original data of height and weight were drawn into growth curves charts by Graphpad Prism 5.0 software according to the different age groups. The children were classified into five age groups: 0-3 months, 4-6 months, 7-12 months, 13-24 months, and 2-7 years. RESULTS: The average birth weight was 3.3 kg and the height averaged 50 cm. The average monthly weight gain was 1.0-1.2 kg and the average monthly increase of height was 4 cm in the 0-3 months group. By 3 months of age, the weight and height averaged 6.6 kg and 62 cm, respectively. In the 4-6 months group, the growth rate was reduced to a half of the 0-3 months group, with an average monthly weight and height gain was 0.5-0.6 kg and 2 cm respectively. The growth rate in the 7-2 months group was a half of the 4-6 months group. By 12 months of age, the weight and height average 9.9 kg and 75 cm, respectively. The average monthly weight and height gain in the 13-24 months group was 0.2 kg and 1 cm respectively, with an average weight and height of 12 kg and 87 cm respectively by 24 months of age. A steady growth was found in the 2-7 years group, with a yearly average weight and height increment of about 2 kg and 7 cm respectively. The formulas for approximate average weight and height in children between 2 and 7 years were as follows: age (yr)*2+8 (kg) (weight); age (yr)*7+75 (cm) (height). CONCLUSIONS: The approximate weight and height of normal Chinese children under 7 years of age can be evaluated by the key parameters and formulas above mentioned.