Pure-Shift-Based Proton Magnetic Resonance Spectroscopy for High-Resolution Studies of Biological Samples.

Proton magnetic resonance spectroscopy (1H MRS) presents a powerful tool for revealing molecular-level metabolite information, complementary to the anatomical insight delivered by magnetic resonance imaging (MRI), thus playing a significant role in in vivo/in vitro biological studies. However, its further applications are generally confined by spectral congestion caused by numerous biological metabolites contained within the limited proton frequency range. Herein, we propose a pure-shift-based 1H localized MRS method as a proof of concept for high-resolution studies of biological samples. Benefitting from the spectral simplification from multiplets to singlet peaks, this method addresses the challenge of spectral congestion encountered in conventional MRS experiments and facilitates metabolite analysis from crowded NMR resonances. The performance of the proposed pure-shift 1H MRS method is demonstrated on different kinds of samples, including brain metabolite phantom and in vitro biological samples of intact pig brain tissue and grape tissue, using a 7.0 T animal MRI scanner. This proposed MRS method is readily implemented in common commercial NMR/MRI instruments because of its generally adopted pulse-sequence modules. Therefore, this study takes a meaningful step for MRS studies toward potential applications in metabolite analysis and disease diagnosis.

CTCOSY-JRES: A high-resolution three-dimensional NMR method for unveiling J-couplings.

Two-dimensional (2D) J-resolved spectroscopy provides valuable information on J-coupling constants for molecular structure analysis by resolving one-dimensional (1D) spectra. However, it is challenging to decipher the J-coupling connectivity in 2D J-resolved spectra because the J-coupling connectivity cannot be directly provided. In addition, 2D homonuclear correlation spectroscopy (COSY) can directly elucidate molecular structures by tracking the J-coupling connectivity between protons. However, this method is limited by the problem of spectral peak crowding and is only suitable for simple sample systems. To fully understand the intuitive coupling relationship and coupling constant information, we propose a three-dimensional (3D) COSY method called CTCOSY-JRES (Constant-Time COrrelation SpectroscopY and J-REsolved Spectroscopy) in this paper. By combining the J-resolved spectrum with the constant-time COSY technique, a doubly decoupled COSY spectrum can be provided while preserving the J-coupling constant along an additional dimension, ensuring high-resolution analysis of J-coupling connectivity and J-coupling information. Moreover, compression sensing and fold-over correction techniques are introduced to accelerate experimental acquisition. The CTCOSY-JRES method has been successfully validated in a variety of sample systems, including industrial, agricultural, and biopharmaceutical samples, revealing complex coupling interactions and providing deeper insights into the resolution of molecular structures.

Association of sarcopenia with osteoporosis in Chinese patients with type 2 diabetes.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) present a higher tendency to develop sarcopenia and osteoporosis compared with the normal population. Currently, osteoporosis screening has been frequently performed among T2DM patients, but sarcopenia screening is relatively less, and the association between the two diseases remains unclear. Herein, this study aims to determine the association between sarcopenia and osteoporosis in Chinese T2DM patients. METHODS: This was a retrospective study of 678 patients with T2DM in the First Affiliated Hospital of Wenzhou Medical University. The bone mineral density (BMD) and muscle mass were measured by using dual-energy X-ray absorptiometry scanning. The diagnostic criteria of sarcopenia referred to the consensus by the Asia Working Group for Sarcopenia (AWGS). RESULT: Among T2DM patients, the proportion of the sarcopenia population complicated with osteoporosis was higher than that of the non-sarcopenia (30.9% vs. 8.6% in men and 46.9% vs. 33.9% in women), but only significantly in men. The BMD of the hip and femoral neck was positively correlated with skeletal muscle mass index (SMI), grip strength, and gait speed (P < 0.01). After adjusting all covariates, the association between sarcopenia and BMD showed odds ratios of 0.43 (95% CI:0.28-0.66) for the femoral neck and 0.49 (95% CI:0.32-0.73) for the hip. CONCLUSIONS: The BMD of the hip and femoral neck in T2DM patients is related to sarcopenia-related indicators and represents an independent protective factor for sarcopenia. To reduce the risk of falls, fractures, and weakness, it is necessary to take sarcopenia assessment in people with T2DM and osteopenia/osteoporosis.

Electrochemical immuno-biosensors for the detection of the tumor marker alpha-fetoprotein: A review.

Alpha-fetoprotein (AFP) is a glycoprotein that has many important physiological functions, including transportation, immunosuppression, and induction of apoptosis by T lymphocytes. AFP is closely related to the development of hepatocellular carcinoma and many kinds of tumors, all of which can show high concentrations, so it is used as a positive test indicator for many kinds of tumors. This paper reviews recent advances in the detection of the tumor marker AFP based on three immuno-biosensors: electrochemical (EC), photoelectrochemical (PEC), and electrochemical luminescence (ECL). The electrodes are modified by different materials or homemade composites, different signaling molecules are selected as single probes or dual probes for the detection of AFP. The detection limit was as low as 3 fg/mL, which indicated that the AFP immunosensor had achieved highly sensitive detection. In addition, we also reviewed and summarized the current development status and application prospect of AFP immunoelectrochemical sensors. There are not too many researches on immunosensors based on dual-signal ratios, and the commonly used probes are methylene blue (MB) and ferrocene (Fc). It would be more innovative to have more novel signaling molecules as probes to prepare dual-signal ratio sensors.

Electrochemical sensor for ultrasensitive sensing of biotin based on heme conjugated with gold nanoparticles and its electrooxidation mechanism.

We report the fabrication of a facile sensor using heme conjugated with gold nanoparticles (AuNPs) in situ on a glass carbon electrode (GCE) for the ultrasensitive determination of biotin without antibody or streptavidin. The use of heme and AuNPs as dual amplifiers allows a very broad detection range from 0.0050 to 50.0000 µmol·L-1 and a very low detection limit of 0.0016 µmol·L-1. The mechanistic aspects were elucidated using electrochemical analyses and frontier orbital calculations showing that the electrooxidation of biotin involves a one-electron and a one-proton transfer, generating biotin sulfoxide. The heme/AuNPs/GCE sensor exhibited excellent selectivity, reproducibility and stability, indicating high robustness. The recovery was between 97.20 and 105.70% with RSD less than 8.71%, suggesting good practicability. Our studies demonstrate that this approach can be used to detect and quantify biotin in a range of foods, including milk, infant formula, flour, orange juice, mango juice, egg white and egg yolk. Furthermore, all measurements do not require any intricate preparation or pre-treatment of the foods, thus representing a great potential for point-of-care testing.

A facile indole probe for ultrasensitive immunosensor fabrication toward C-reactive protein sensing.

C-reactive protein (CRP) is a protein biomarker for acute phase response. Herein, we fabricate a highly sensitive electrochemical immunosensor for CRP on a screen-printed carbon electrode (SPCE) with indole as a novel electrochemical probe and Au nanoparticles for signal amplification. Amongst, indole appeared as transparent nanofilms on the electrode surface, and underwent a one-electron and one-proton transfer to form oxindole during the oxidation process. Upon optimization of experimental conditions, a logarithmic correlation between CRP concentration (0.0001-100 µg∙mL-1) and response current was revealed with a detection limit of 0.03 ng∙mL-1 and a sensitivity of 5.7055 µA∙µg-1∙mL∙cm-2. The sensor exhibited exceptionally distinction selectivity, reproducibility and stability of the electrochemical immunosensor studied. The recovery rate of CRP in human serum samples determined by the standard addition method, ranged between 98.2-102.2%. Overall, the developed immunosensor is promising, and has the potential for CRP detection in real human serum samples.

Facile bimetallic co-amplified electrochemical sensor for folic acid sensing based on CoNPs and CuNPs.

Folic acid (FA) is essential for human health, particularly for pregnant women and infants. In this work, a glassy carbon electrode (GCE) was modified by a bimetallic layer of Cu/Co nanoparticles (CuNPs/CoNPs) as a synergistic amplification element by simple step-by-step electrodeposition, and was used for sensitive detection of FA. The proposed CuNPs/CoNPs/GCE sensor was characterized by differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS) and field emission scanning electron microscopy (FESEM). Then, under optimal conditions, a linear relationship was obtained in the wide range of 110.00-1750.00 µM for the detection of FA with a limit of detection (LOD) of 34.79 µM (S/N = 3). The sensitivity was calculated as 0.096 µA µM-1 cm-2. Some interfering compounds including glucose (Glc), biotin, dopamine (DA), and glutamic acid (Glu) showed little effect on the detection of FA by amperometry (i-t). Finally, the average recovery obtained was in a range of 91.77-110.06%, with a relative standard deviation (RSD) less than 8.00% in FA tablets, indicating that the proposed sensor can accurately and effectively detect the FA content in FA tablets.

Enzyme-free glucose sensors with efficient synergistic electro-catalysis based on a ferrocene derivative and two metal nanoparticles.

Gold electrodes (GE) were modified by the deposition of copper nanoparticles (CuNPs) and cobalt nanoparticles (CoNPs), followed by drop-casting of the ferrocene derivative FcCO-Glu-Cys-Gly-OH (Fc-ECG), resulting in two enzyme-free electrochemical sensors Fc-ECG/CuNPs/GE and Fc-ECG/CuNPs/GE. The ferrocene-peptide conjugate acts as an effective redox mediator for glucose oxidation, while metal nanoparticles acted as non-biological sites for glucose oxidation. Field emission scanning electron microscopy (FESEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were carried out for characterization, while differential pulse voltammetry (DPV) was used for glucose quantification. Under optimized conditions, DPV shows a linear relationship between glucose concentration and the peak current. Both sensors showed a surprisingly high sensitivity of 217.27 and 378.70 µA mM-1 cm-2, respectively. A comparison to other glucose sensors shows a sensitivity that is 25 times higher. The sensors exhibit good reproducibility, stability, and repeatability. In injection experiments, recovery rates were 87.39-107.65% and 100.00-106.88%, respectively.

One step construction of an electrochemical sensor for melamine detection in milk towards an integrated portable system.

Excessive intake of melamine (MEL) can be harmful to human health, and it is important to establish a rapid and accurate MEL detection method. As the electrochemical activity of MEL is very low, ferrocenylglutathione (Fc-ECG) was used as an electron transfer mediator to assist with the detection of MEL using screen-printed carbon electrode (SPCE). This modified electrode (MEL/Fc-ECG/SPCE) was prepared by stepwise drop-casting and was fully characterized. Results showed that MEL significantly enhanced signal of Fc-ECG/SPCE sensor due to the three p-π conjugated double bonds that facilitated electron transfer. Under optimal conditions, the sensor exhibits two linearities in the range of 0.20-2.00 µM and 8.00-800 µM, with a sensitivity of 15.03 µA·µM-1·cm-2. The selectivity, stability, and reproducibility were investigated and successfully used to detect MEL in raw milk and confirms safety verification of foods. Moreover, a portable testing platform was designed for MEL detection based on a CH32 chip.

Convenient Heme Nanorod Modified Electrode for Quercetin Sensing by Two Common Electrochemical Methods.

Quercetin (Qu) is one of the most abundant flavonoids in the human diet. High concentrations of Qu can easily cause adverse effects and induce inflammation, joint pain and stiffness. In this study, Heme was used as a sensitive element and deposited and formed nanorods on a glassy carbon electrode (GCE) for the detection of Qu. The Heme/GCE sensor was characterized using scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques. Under optimized conditions, the developed sensor presented a linear concentration ranging from 0.1 to 700 µmol·L-1 according to the CV and DPV methods. The detection limit for the sensor was 0.134 µmol·L-1 and its sensitivity was 0.12 µA·µM-1·cm-2, which were obtained from CV analysis. Through DPV analysis we obtained a detection limit of 0.063 µmol·L-1 and a sensitivity of 0.09 µA·µM-1·cm-2. Finally, this sensor was used to detect the Qu concentration in loquat leaf powder extract, with recovery between 98.55-102.89% and total R.S.D. lower than 3.70%. The constructed electrochemical sensor showed good anti-interference, repeatability and stability, indicating that it is also usable for the rapid detection of Qu in actual samples.

Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas.

BACKGROUND: The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions. AIM: To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas. METHODS: This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas. RESULTS: Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043). CONCLUSION: H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.

Real-Time Electrochemical Detection of Uric Acid, Dopamine and Ascorbic Acid by Heme Directly Modified Carbon Electrode.

Several simple electrochemical sensors were designed for three analytes, uric acid (UA), dopamine (DA) and ascorbic acid (AA) detection via electrolytic deposition of three functional materials heme, Fc(Cys)2 and Fc-ECG onto glassy carbon electrodes (GCEs) without other medium. Characterization of the modified GCEs was conducted using SEM, TEM and DPV methods. Results showed that the heme/GCE demonstrated notable electro-catalytic capabilities, towards DA, AA, and UA oxidation in a solution of phosphate buffer. The current signals of DPV technique for three analytes shown up three defined oxidated peaks, the peak potential differences was 192 mV for AA and DA, and 142 mV for DA and UA. Under optimal conditions, it can be obtained linear responses for AA, DA and UA in the following concentration ranges: 10 to 50, 5 to 20, and 2.5 to 20 µmol·L-1, and the limits of detection was calculated as 0.76, 0.50 and 0.63 µmol·L-1, respectively. The results demonstrated that the heme directly modified GCE was a well-suited electrochemical sensor for determining UA, DA and AA in actual samples.

The construction of a simple sensor for the simultaneous detection of nitrite and thiosulfate by heme catalysis.

Several simple sensors were fabricated through a one-step method. By depositing electro-active compounds, such as ß-cyclodextrins (ß-CD), heme, dopamine (DA), or Fc-ECG, onto a screen-printed electrode (SPE), the successful simultaneous detection of nitrite (NO2 -) and thiosulfate (S2O3 2-) ions was observed. Under optimal operating conditions, the notable electrocatalytic abilities of a Heme/SPE sensor were detected for the oxidation of NO2 - and S2O3 2-, with remarkable peak potential differences, after characterization via SEM, CV, and DPV. Linear relationships were obtained in the ranges of 5.0-200.0 µmol L-1 and 1.0-100.0 µmol L-1 for the current response versus concentration of NO2 - and S2O3 2-, respectively. The limits of detection were determined to be 1.67 and 0.33 µmol L-1 while the sensitivities of detection were noted to be 0.43 and 1.43 µA µM-1 cm-2, respectively. During the detection of NO2 - and S2O3 2-, no interfering common ions were observed. Furthermore, average recoveries from 96.0 to 104.3% and a total R.S.D. of less than 3.1% were found for the detection of NO2 - and S2O3 2- in pickled juice and tap water using the simple sensor. These results showed that rapid and precise measurements for actual application in NO2 - and S2O3 2- detection could be conducted in food samples, indicating a potential use in food safety.

Doped N/Ag Carbon Dot Catalytic Amplification SERS Strategy for Acetamiprid Coupled Aptamer with 3,3'-Dimethylbiphenyl-4,4'-diamine Oxidizing Reaction.

The as-prepared co-doped N/Ag carbon dot (CDNAg) has strong catalysis of H2O2 oxidation of 3,3'-dimethylbiphenyl-4,4'-diamine (DBD). It forms an oxidation product (DBDox) with surface-enhanced Raman scattering (SERS) activity at 1605 cm-1 in the silver nanosol substrate, and a CDNAg catalytic amplification with SERS analytical platform can be structured based on aptamer (Apt) with the DBD oxidizing reaction. For example, the aptamer (Apt) of acetamiprid (ACT) can be adsorbed on the surface of CDNAg, resulting in inhibited catalytic activity, the reduced generation of DBDox, and a weakened SERS intensity. When the target molecule ACT was added, it formed a stable Apt-ACT complex and free CDNAg that restored catalytic activity and linearly enhanced the SERS signal. Based on this, we proposed a new quantitative SERS analysis method for the determination of 0.01⁻1.5 µg ACT with a detection limit of 0.006 µg/L.

A Facile Electrochemical Sensor Labeled by Ferrocenoyl Cysteine Conjugate for the Detection of Nitrite in Pickle Juice.

Simple and facile electrochemical sensors for nitrite detection were fabricated by directly depositing ferrocenoyl cysteine conjugates Fc[CO-Cys(Trt)-OMe]2 [Fc(Cys)2] or Fc[CO-Glu-Cys-Gly-OH] [Fc-ECG] on screen-printed electrodes (SPEs). The modified carbon electrodes were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Results indicated that Fc-ECG/SPE sensor showed enhanced current response and a lower overpotential than Fc(Cys)2/SPE sensor for nitrite detection. Optimal operating conditions were estimated for nitrite detection by DPV. The concentration of nitrite showed a good linear relationship with the current response in the range of 1.0⁻50 µmol·L-1 and with 0.3 µmol·L-1 as the concentration for limit of detection. There were no interferences from most common ions. The development of this electrochemical sensor was used for nitrite detection in pickled juice with a R.S.D. lower than 2.1% and average recovery lower than 101.5%, which indicated that disposable electrochemical sensor system can be applied for rapid and precise nitrite detection in foods.

A sensitive and selective electrochemical biosensor for the determination of beta-amyloid oligomer by inhibiting the peptide-triggered in situ assembly of silver nanoparticles.

Soluble beta-amyloid (Aß) oligomer is believed to be the most important toxic species in the brain of Alzheimer's disease (AD) patients. Thus, it is critical to develop a simple method for the selective detection of Aß oligomer with low cost and high sensitivity. In this paper, we report an electrochemical method for the detection of Aß oligomer with a peptide as the bioreceptor and silver nanoparticle (AgNP) aggregates as the redox reporters. This strategy is based on the conversion of AgNP-based colorimetric assay into electrochemical analysis. Specifically, the peptide immobilized on the electrode surface and presented in solution triggered together the in situ formation of AgNP aggregates, which produced a well-defined electrochemical signal. However, the specific binding of Aß oligomer to the immobilized peptide prevented the in situ assembly of AgNPs. As a result, a poor electrochemical signal was observed. The detection limit of the method was found to be 6 pM. Furthermore, the amenability of this method for the analysis of Aß oligomer in serum and artificial cerebrospinal fluid (aCSF) samples was demonstrated.

Transcutaneous acupoint electrical stimulation pain management after surgical abortion: A cohort study.

INTRODUCTION: Transcutaneous acupoint electrical stimulation (TEAS) is a standard therapy for painful conditions. This study evaluated pain-relieving effects of treatment with TEAS before and after surgical abortion. METHODS: In this cohort study 140 nulliparae requesting pregnancy termination with intravenous anesthesia from August to December 2013 at the outpatient clinic of Wenzhou Medical University First Affiliated Hospital were recruited and divided into three cohorts who received TEAS pre-, post-, and both pre- and post-operation, alongside a control group. The cohorts underwent TEAS treatment for 30 min before and/or after the procedure while the control group received no TEAS treatment. Pain levels were evaluated upon recovery at 10, 30, and 45 min, respectively, after abortion. RESULTS: Mean Visual Analog Scale (VAS) scores in pre-operation cohorts, but not the post-operation cohort, were significantly lower than those obtained for the control group at 10 min (p < 0.01). VAS scores at 30 min and 45 min postoperatively were similar in each cohort but lower than control values (p < 0.001). More cohort patients reported mild or no pain than control patients (p < 0.05); the pre-operation cohorts had more women with no pain compared with the post-operation group (p < 0.05). There were no differences among groups in medical treatment required after 45 min. There were fewer complications of nausea and vomiting in the cohorts compared with the control group (p < 0.05). CONCLUSIONS: Performing TEAS before and after surgical abortion provides postoperative pain relief. However, receiving TEAS before surgery allowed more women to experience mild or no pain. IMPLICATIONS: Transcutaneous acupoint electrical stimulation shows potential as an adjunct to conventional pain treatment following surgical abortion in nulliparae.

Determination of Residual Solvents in Linezolid by Static Headspace GC.

A headspace gas chromatographic method was developed for the determination of residual solvents in linezolid active substances. The solvents include petroleum ether (60-90°C), acetone, tetrahydrofuran, ethyl acetate, methanol, dichloromethane (DCM) and pyridine. The method showed the possibility to detect the tested solvents with a linear determination correlation coefficient (r) greater than 0.9995 except for petroleum ether (0.9980). The limits of detection ranged between 0.12 µg/mL (petroleum ether) and 3.56 µg/mL (DCM), and the limits of quantity ranged between 0.41 µg/mL (petroleum ether) and 11.86 µg/mL (DCM). The method achieved good accuracy (recoveries ranging from 92.8 to 102.5%) and precision for both run-to-run and day-to-day assay (relative standard deviation ranging from 0.4 to 1.3%) for all seven solvents concerned, which were applied in the quality control of three batches of linezolid successfully.

Interaction Study of Ferrocene Derivatives and Heme by UV-Vis Spectroscopy.

The interaction between ferrocene derivatives, such as Fc(COOH)2(λmax=286 nm), Fc(OBt)2(λmax=305 nm), Fc(Cys)(λmax=289 nm) and heme(λmax=386 nm) were studied by UV-Vis spectroscopy, respectively. The results show that, when the concentration of heme is fixed, the absorbance of heme increases with the increase of Fc(COOH)2 and Fc(Cys) concentration, the absorbance of heme almost keep the same when Fc(OBt)2 concentration increases; when the concentration of ferrocene derivatives are fixed, the absorbance of Fc(COOH)2 and Fc(Cys) also increases with the increase of heme concentration, the absorbance of Fc(OBt)2 almost keep the same when heme concentration increase. It is demonstrated that the hydrogen bonding interactions happen between Fc(COOH)2, Fc(Cys) and heme, none of Fc(OBt)2, the formation of hydrogen bonding lead to the growth of molecular chain, the bigger molecule can absorb more energy and increase the absorbance. Meanwhile, the stability of molecule is affected by the formation of hydrogen bonding, when the reaction time increases from 0.5 h to 18 h and 48 h, the absorbance at λmax=384 nm change from 2.64 to 2.53 and 2.51 with fixed concentration of Fc(COOH)2, the absorbance at λmax=384 nm change from 1.76 to 1.72 and 1.68 with fixed concentration of heme, the absorbance at λmax=397 nm change from 2.74 to 2.63 and 2.55 with fixed concentration of Fc(Cys), and the absorbance at λmax=397 nm change from 1.82 to 1.58 and 1.49 with fixed concentration of heme, respectively.

Polymorphism of flucloxacillin sodium.

The polymorphism of flucloxacillin sodium has not been discussed sufficiently so far. Flucloxacillin sodium which was crystallized with different solvents, was found to exist in amorphism and three crystal forms (I, II, III). This results were confirmed by infra-red (IR) spectra, thermogravimetry (TG), X-ray diffraction analysis (XRD) and equilibrium solubility. It is noticed that form III has very good solubility in phosphate buffer solution, with an average solubility of 0.86 g (20-40 degrees C). However, more efforts are needed to carry out and decide whether this form can be used for industrial production.