Small Extracellular Vesicles Laden Oxygen-Releasing Thermosensitive Hydrogel for Enhanced Antibacterial Therapy against Anaerobe-Induced Periodontitis Alveolar Bone Defect.

Periodontitis is a bacterially induced chronic destructive inflammatory disease that leads to irreversible destruction of the tooth supporting structure, including connective tissue destruction, bone resorption, and even tooth loss. Until now, there has been no effective treatment to repair inflammatory bone loss in periodontitis. Recently, small extracellular vesicles (sEVs) emerged as the essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. However, limitations of antimicrobial activity associated with the use of sEVs have led to the urgency of new alternative strategies. Currently, we investigated the potential of a biocompatible oxygen-releasing thermosensitive hydrogel laded with sEVs secreted by bone marrow MSCs (BMMSCs) for the alveolar bone defect in periodontitis. The hydrogel composed of different polymers such as chitosan (CS), poloxamer 407 (P407), and cross-linked hyaluronic acid (c-HA) conglomerating is a kind of nanoporous structure material. Then, the gel matrix further encapsulated sEVs and calcium peroxide nanoparticles to realize the control of sEVs and oxygen release. Furthermore, ascorbic acid was added to achieve the REDOX equilibrium and acid-base equilibrium. The experiments in vivo and in vitro proved its good biocompatibility and effectively inhibited the growth of the periodontal main anaerobe, relieved periodontal pocket anaerobic infections, and promoted the periodontal defect regeneration. Therefore, this finding demonstrated that it was a promising approach for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria-induced infections, for future clinical application.

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial.

Background: Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Methods: Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L or non-FH patients with screening LDL-C level ≥3.4 mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450 mg Q4W, tafolecimab 600 mg Q6W, placebo 450 mg Q4W, or placebo 600 mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Findings: A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n = 411) or placebo (n = 203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]: -65.0% [97.5% CI: -70.2%, -59.9%] for 450 mg Q4W; -57.3% [97.5% CI: -64.0%, -50.7%] for 600 mg Q6W; both P < 0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8 mmol/L, and LDL-C < 1.4 mmol/L than placebo group at both dose regimens (all P < 0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Interpretation: Tafolecimab dosed at 450 mg Q4W and 600 mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. Funding: This study was sponsored by Innovent Biologics, Inc.

Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial.

Background: Tafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia. Objectives: The purpose of this study was to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. Methods: Patients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Results: A total of 303 patients were enrolled and received at least 1 dose of tafolecimab (n = 205) or placebo (n = 98). The least squares mean percent change in LDL-C level from baseline to week 12 was -68.9% (SE 1.4%) in the tafolecimab group and -5.8% (1.8%) in the placebo group (difference: -63.0%; [95% CI: -66.5% to -59.6%]; P < 0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than did those in the placebo group (all P < 0.0001). Furthermore, tafolecimab markedly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. During the double-blind treatment period, the most commonly reported adverse events included urinary tract infection (5.9% with tafolecimab vs 4.1% with placebo) and hyperuricemia (3.4% vs 4.1%). Conclusions: Tafolecimab was safe and showed robust lipid-lowering efficacy in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. (A Study of IBI306 in Participants With Hypercholesterolemia; NCT04709536).

Icosapent ethyl therapy for very high triglyceride levels: a 12-week, multi-center, placebo-controlled, randomized, double-blinded, phase III clinical trial in China.

OBJECTIVES: Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. METHODS: Patients having TG levels (5.6-22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). RESULTS: Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups. CONCLUSIONS: IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.

A Nomogram for Predicting Survival in Patients With Colorectal Cancer Incorporating Cardiovascular Comorbidities.

Background: Cardiovascular comorbidities (CVCs) affect the overall survival (OS) of patients with colorectal cancer (CRC). However, a prognostic evaluation system for these patients is currently lacking. Objectives: This study aimed to develop and validate a nomogram, which takes CVCs into account, for predicting the survival of patients with CRC. Methods: In total, 21,432 patients with CRC were recruited from four centers in China between January 2011 and December 2017. The nomogram was constructed, based on Cox regression, using a training cohort (19,102 patients), and validated using a validation cohort (2,330 patients). The discrimination and calibration of the model were assessed by the concordance index and calibration curve. The clinical utility of the model was measured by decision curve analysis (DCA). Based on the nomogram, we divided patients into three groups: low, middle, and high risk. Results: Independent risk factors selected into our nomogram for OS included age, metastasis, malignant ascites, heart failure, and venous thromboembolism, whereas dyslipidemia was found to be a protective factor. The c-index of our nomogram was 0.714 (95% CI: 0.708-0.720) in the training cohort and 0.742 (95% CI: 0.725-0.759) in the validation cohort. The calibration curve and DCA showed the reliability of the model. The cutoff values of the three groups were 68.19 and 145.44, which were also significant in the validation cohort (p < 0.001). Conclusion: Taking CVCs into account, an easy-to-use nomogram was provided to estimate OS for patients with CRC, improving the prognostic evaluation ability.

YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects.

PURPOSE: Polo-like kinase 4 (PLK4), a member of the polo-like kinase family, plays several important roles in mitotic regulation, including centrosome duplication, spindle formation, and cytokinesis. PLK4 overexpression is frequently detected in many human cancers, including ovarian cancer, and the inhibition of PLK4 activity results in cancer cell mitotic arrest and apoptosis. Therefore, PLK4 might be a valid therapeutic target for antitumor therapy. In the present study, we aimed to determine if YLZ-F5, a potent small-molecule inhibitor of PLK4, inhibits ovarian cancer cell growth. METHODS AND RESULTS: MTT assay showed that YLZ-F5 inhibited ovarian cancer cell proliferation in a concentration- and time-dependent manner. The results of colony formation assays were consistent with those of the MTT assay results. In addition, YLZ-F5 induced ovarian cancer cell apoptosis that was associated with activation of caspase-3/caspase-9. Moreover, YLZ-F5 caused aberrant in centriole duplication that was associated with the inhibition of PLK4 phosphorylation. Notably, we showed that YLZ-F5 promoted the accumulation of ovarian cancer cells with mitotic defects (> 4 N DNA content) in a concentration-dependent manner. Furthermore, YLZ-F5 markedly inhibited the migration of A2780 cells. CONCLUSION: Taken together, these findings suggest that YLZ-F5 is a potential drug candidate for human ovarian cancer.

BMP4 promotes hepatocellular carcinoma proliferation by autophagy activation through JNK1-mediated Bcl-2 phosphorylation.

BACKGROUND: Autophagy is a conserved catabolic process with complicated roles in tumor development. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF-ß) family of regulatory proteins, plays a crucial role in human malignancies. However, whether BMP4 contributes to the regulation of autophagy in hepatocellular carcinoma (HCC) progression remains elusive. METHODS: Functional analysis of BMP4 on HCC proliferation and autophagy was performed both in vitro and in vivo in HepG2 and HCCLM3 cells. Autophagic activity was estimated by Western blot for autophagic marker proteins and by transmission electron microscopy (TEM). Transfection of mRFP-GFP-LC3 adenovirus was applied to observe autophagic flux and high content screening was used for quantification. The signaling pathway of BMP4-regulated HCC proliferation and autophagy was investigated by Western blot. RESULTS: BMP4 treatment promoted HCC cells proliferation and induced autophagy. The in vivo xenograft model supported that BMP4 overexpression promoted the growth of HCC cells and autophagy induction while BMP4 knockdown exerted the opposite effect. 3-MA pre-treatment or knockdown of Beclin-1 (BECN1) blocked HCC autophagy by decreasing the expression of LC3-II and subsequently attenuated BMP4-induced autophagy and cells proliferation enhanced by BMP4 in vitro and in vivo. Mechanistic study revealed that the induction of autophagy by BMP4 was mediated through activating the JNK1/Bcl2 pathway. Furthermore, the JNK1 inhibitor and knockdown of JNK1 could attenuate autophagy induced by BMP4 and eliminated BMP4-promoted HCC cells growth. CONCLUSIONS: BMP4 promoted HCC proliferation by autophagy activation through JNK1/Bcl-2 signaling.

BMP4 promotes oxaliplatin resistance by an induction of epithelial-mesenchymal transition via MEK1/ERK/ELK1 signaling in hepatocellular carcinoma.

BACKGROUND: Bone morphogenetic protein-4 (BMP4) is a key regulator of epithelial-mesenchymal transition (EMT), which is crucial for cancer cells to acquire chemoresistance. The effects of BMP4 on OXA sensitivity in HCC need to be elucidated. METHODS: Functional analysis of BMP4 on EMT-regulated OXA sensitivity was performed in human HCC specimens, in the HCC cell lines HepG2 and HCCLM3, and in a subcutaneous tumor model receiving OXA treatment. The downstream signaling targets of BMP4 in HCC were profiled and confirmed. RESULTS: BMP4 expression was significantly increased in HCC tissue, and was correlated with tumor de-differentiation and unfavorable prognosis. BMP4 promoted HCC EMT and was correlated with OXA resistance. Blocking of BMP4 reversed EMT and increased OXA chemosensitivity in vitro and in vivo. ELK1, a transcription factor involved in EMT, was an important mediator of BMP4-induced OXA resistance in HCC. Blocking of MEK/ERK/ELK1 attenuated BMP4-induced EMT and enhanced OXA sensitivity. CONCLUSIONS: BMP4 induces EMT and OXA chemoresistance via MEK/ERK/ELK1 signaling pathway in HCC. BMP4 may be a valuable therapeutic target for HCC patients receiving OXA-based chemotherapy.

BMP4 enhances hepatocellular carcinoma proliferation by promoting cell cycle progression via ID2/CDKN1B signaling.

Bone morphogenetic protein-4 (BMP4) plays a crucial role in carcinogenesis, but the effects and signaling mechanisms of BMP4 in hepatocellular carcinoma (HCC) are not clearly clarified. The present study aimed to identify the roles of BMP4 in the proliferation of human HCC. In this study, BMP4 expression and its correlation with clinicopathological characteristics and the survival of HCC patients were analyzed in two independent cohorts consisting of 310 subjects. Functional analysis of BMP4 on HCC proliferation was performed in vitro and in vivo in human HCC specimens, HCC cells of Bel-7402 and HCCLM3, and subcutaneous tumor model. The downstream signaling targets of BMP4 in HCC were investigated by PCR Array and Western blot. The results indicated that BMP4 expression was significantly increased in HCC tissues and closely related with unfavorable prognosis of HCC. BMP4 treatment increased cell proliferation and promoted G1/S cell cycle progression. In vivo subcutaneous tumor of nude mice model supported that BMP4 overexpression promoted the growth of HCC cells and BMP4 knockdown hold the opposite trend. Id2 was directly upregulated by BMP4, resulting in the mediated expression of cell cycle regulatory protein of CDKN1B. Blocking of Id2 attenuated BMP4-induced proliferation, confirming the important roles of Id2 in BMP4-mediated proliferation in HCC. So BMP4 is overexpressed in HCC tissues and acts as a poor prognostic factor of HCC patients. BMP4-induced ID2/CDKN1B signaling facilitates proliferation of HCC.

The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma.

Tumor invasion and chemotherapy resistance, which are associated with epithelial-mesenchymal transition (EMT), remain as major challenges in hepatocellular carcinoma (HCC) treatment. Neferine, a natural component of Nelumbo nucifera, have been proven the antitumor efficiency in cancer, but the effects of Neferine on HCC invasion and chemosensitivity need to be elucidated. Applying multiple assays of cell proliferation, flow cytometry, immunofluorescence staining, qRT-PCR, Western blot, fluorescence molecular tomography imaging, the influences of Neferine on EMT-regulated viability, apoptosis, invasion, and oxaliplatin (OXA) sensitivity were assessed in HCC cells of HepG2 and Bel-7402, as well as in xenograft animal models in vivo. Here, we reported that Neferine had no obvious effects on HCC cells proliferation, but significantly enhanced cytotoxicity and apoptosis caused by OXA in vitro and in vivo. Through an upregulation of E-cadherin and downregulation of Vimentin, Snail and N-cadherin, Neferine suppressed EMT-induced migration and invasion abilities of HCC cells. TGF-ß1 cancelled the effects of Neferine on the migration and invasion of HCC cells. Snail overexpression or TGF-ß1-induced EMT attenuated Neferine-mediated OXA sensitization in HCC. Together, our data suggest that Neferine enhances oxaliplatin sensitivity through an inhibition of EMT in HCC cells. Neferine may be used as an OXA sensitizer in HCC chemotherapy.

Integrin-linked kinase overexpression promotes epithelial-mesenchymal transition via nuclear factor-κB signaling in colorectal cancer cells.

AIM: To investigate the effect of integrin-linked kinase (ILK) on proliferation, metastasis, and invasion of the colorectal cancer cell line SW480. METHODS: In this study, the colorectal cancer cell line SW480 was stably transfected with ILK plasmids, and small interfering RNA (siRNA) was used to knockdown expression of nuclear factor (NF)-κB/p65. Methylthiazole tetrazolium (MTT) assay was performed to measure proliferation, and the wound healing migration assay and matrigel invasion assay were used to test the metastasis and invasion ability of SW480 cells. To explore the epithelial-mesenchymal transition (EMT) process, embryonic development, and the invasion and metastasis of tumors, the protein level of E-cadherin, vimentin, snail, and slug was detected by western blot. Immunofluorescence was also used to detect E-cadherin expression. Western blot was used to determine the level of phosphorylated-inhibitor of kappa B (IκB)a, inhibitor of gamma B (IγB)a, and nuclear factor kappa B (NF-κB) expressions and to explore the ILK signaling pathway. RESULTS: Western blot results revealed that ILK expression significantly increased when ILK was overexpressed in SW480 cells (P < 0.05). Proliferation, metastasis, and invasion ability were improved in the vector-ILK group compared to the vector group (P < 0.05). Immunofluorescence results revealed that E-cadherin fluorescence intensity decreased after ILK was overexpressed (P < 0.05). Western blot results revealed that the protein expression of E-cadherin was reduced, while vimentin, snail, and slug were upregulated when ILK was overexpressed in SW480 cells (P < 0.05). In order to determine the role of the NF-κB signaling pathway in ILK overexpression promoted EMT occurrence, we overexpressed ILK in SW480 cells and found that levels of NF-κB/p65 and cytoplasmic phosphorylated-IκBa were increased and that cytoplasmic IкBa levels were decreased compared to the control group (P < 0.05). Furthermore, NF-κB/p65 knockout revealed that E-cadherin was increased in the overexpressed ILK group. CONCLUSION: ILK overexpression improved the proliferation, metastasis, and invasion ability of SW480 cells, and this effect may be mediated by the NF-κB signaling pathway.

[Expression of RASAL2 in hepatocellular carcinoma and the clinical significance].

OBJECTIVE: To detect the expression of RA SAL2 in patients with hepatocellular carcinoma (HCC), and to investigate the association of RASAL2 expression with pathological characteristics and prognosis. METHODS: Immunohistochemical SP method was used to detect the expression of RA SAL2 in 164 samples of HCC tissue and the adjacent tissue. Th e association of RA SAL2 expression with clinical features and prognosis was analyzed. RESULTS: The expression of RASAL2 in adjacent tissue was significantly increased compared to that in HCC tissue (P<0.001). The expression level of RASAL2 was associated with the degree of differentiation, tumor TNM stage and vascular invasion (P<0.001), but not associated with the level of AFP, tumor size, or the number of nodules (P>0.05). The 5 years recurrence-free survival (RFS) in patients with low expression of RASLA2 was significantly reduced compared with that in patients with high expression of RASLA2 (P<0.001). Cox analysis showed that low expression of RASLA2 was the independent factor for recurrence and death in HCC patients after surgery (P<0.001). CONCLUSION: Low expression of RRASAL2 is significantly associated with the poor prognosis of HCC, which is an independent factor for HCC prognosis.

[Correlation between the expression of C-terminal tensin-like protein and the prognosis of hepatocellular carcinoma].

OBJECTIVE: To explore the correlation between the expression of C-terminal tensin-like protein (CTEN) and the prognosis of hepatocellular carcinoma (HCC). METHODS: Using immunohistochemistry, we detected CTEN protein level in samples of primary lesion and adjacent non-tumor lesion collected from 240 patients with HCC. The relationship between CTEN expression and clinicopathology, 5 year recurrent-free survival, or overall survival was evaluated by Chi-square test, Kaplan-Meier, or Cox regression analysis. RESULTS: High CTEN expression was detected in 55% of hepatocellular carcinoma tissues and 20% of adjacent carcinoma tissues (P< 0.001). CTEN expression was positively correlated with tumor diameter (P=0.022), venous invasion (P=0.007) or TNM stages (P=0.022). Five-year recurrence-free survival time (P< 0.001) and overall survival time (P< 0.001) in patients with high CTEN expression were significantly less than those in patients with low CTEN expression. Multivariate Cox regression analysis revealed that the CTEN expression was an independent prognostic marker for HCC (all P< 0.05). CONCLUSION: CTEN protein may play a role in the genesis and development of HCC, and it can function as a prognostic marker.

[Research on the correlation chart of near infrared spectra by using multiple scatter correction technique].

Correlation spectroscopy can be used to describe the linear correlationship between the absorbance and concentration data in the whole spectra range and clearly figure out the characteristic peak position of the sample under test. Meantime, this chart plays an extremely important role in offering the precise information for choosing the optimal wavelength set during the calibration process. Multiple scatter correct (MSC) spectroscopy is a kind of multiple variable scatter correction technique, and can effectively remove the base shift and tilt phenomenon caused by MSC. As a result, the ratio of signal to noise is improved greatly. Based on this feature, the new idea of the MSC technique was introduced into the preceding data treatment for the creation of correlation chart, and through careful experiment this idea was proved to be correct and effective.

[Analysis of saponin in Chinese ginsengs by NIR spectroscopy].

In the present paper the saponin in Chinese ginseng was analysed quantitatively by using near infrared spectroscopy. The spectral characteristics of the primary ingredients in Chinese ginseng were obtained by applying second derivative, MSC (Multiple Scatter Correction), and correlation chart to the original absorbance spectra of ginseng. Meantime, in combination with the PLS algorithm the calibration process was performed for the quantitative analysis of saponin in Chinese ginseng. The result obtained shows a fine precision of the method, with RMSEC of 0.154% and correlation coefficient of 0.9828.

[Research on the method of choosing optimum wavelengths combination by using multiple scattering correction technique].

Multiple scattering correction(MSC) algorithm can be used effectively to remove the effect of scattering due to the physical factors such as the density and humidity of sample granule, and as a result the ratio of signal to noise is improved greatly. Meantime correlation spectrum plays a important role in the choice of optimum wavelength set because it describes the linear correlationship between the absorbance and concentration of the sample's ingredient under analysis. However, the correlation spectrum obtained by unitary linear regression(ULR) at single wavelength channel can be easily affected by the scattering so as to cover up the characteristic linear information of the sample. In order to solve the problem in the present paper MSC was applied to obtain useful signal and suppress noise of correlation spectrum. Through the careful calibration experiment of ginseng sample this idea has proved to be correct, and satisfactory result was obtained.

[Near infrared determination of the total sugar in Chinese ginsengs].

In the present paper the analysis of the total content of sugar in Chinese ginseng was carried out by using near infrared spectroscopy, and in combination with the PLS algorithm the calibration analysis was performed at the same time. The result shows that the precision obtained through common chemical methods is almost the same as the one through NIR spectroscopy. The SEC (standard error of calibration) is 1.9% and the correlation coefficient is 0.951 7, which proves that this technique is well suitable for rapid quantitative determination of the total content of sugar in Chinese ginseng, and is simple, cheap, and without any chemical pollution, and can present real time result.

[The research to the optimal calibration model for discrete scanning spectrometers].

For spectrometers which don't operate in consistently scanning mode such as fixed-filter spectrometer, diode arrays spectrometer and so on, how to find an optimal wavelengths combination rapidly and accurately has always been a key problem in NIR so far. The conventional methods to choose the optimal wavelengths for calibration are Forward Stepwise multiple linear Regression (FSR) and Backward Stepwise Regression (BSR), which choose the optimal wavelengths based on the t test result of all the calibration wavelengths. However, maybe the wavelength eliminated is very useful in application and the wavelength chosen may not be so useful as expected, as a result it is compulsory to make more tests to verify the truly applicable wavelength combination for calibration. In this paper the combination of the combination-making algorithm in combinatorics and computer languages which operate facing matrix is used to choose the optimal combination of wavelengths for calibration automatically and efficiently by computer. The most robust calibration equation can be obtained by making analysis of calibration regression that operates to find the minimum root mean standard error of calibration.

[The algorithm of eliminating the similar samples in the process of calibration and prediction].

During the manufacture and debugging of the NIR instruments it is compulsory to make final calibration analysis to verify whether the instruments operate correctly. However, the conventional method of NIR calibration needs to make calibration analysis for the instruments with all the samples at hand. In fact in order to cover the samples that will be encountered in the future the amount of the samples set and the labor that the personnel need to offer are enormous. In this paper a new algorithm is presented which can be used to effectively eliminate the similar samples in the original sample set. By using this algorithm we have chosen 94 optimal samples in the original 178 sample set successfully. After performing calibration experiment we found that the sample set chosen by this algorithm are equally representative to the original sample set and obtained almost the same precision compared to the original sample set when the two sample sets were individually calibrated. This algorithm brings great relief to the labor of the workers, presents the possibility of performing more experiments and greatly improves the efficiency of performing calibration experiment. As a result, the amount of calibration sets and the labor of the personnel are reduced remarkably.