ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

AIM:To compare the effects of 0.01% with 0.05% atropine eye drops on pupil diameter(PD)and intraocular pressure(IOP)in myopic children.METHODS: Prospective non-randomized controlled study. A total of 232 myopic children who treated at the Department of Ophthalmology, the Second People's Hospital of Puyang from March 2021 to February 2022 were included. They were divided into 0.01% atropine eye drops group(81 cases), 0.05% atropine eye drops group(77 cases), and control group(74 cases)according to patients' will, respectively. The control group received placebo eye drops(isotonic excipient). The PD and IOP of the three groups of patients were measured before medication and at 6 and 12 mo after medication.RESULTS: Finally, 181 cases(181 eyes)(with all right eye data included in the study)completed a 1-year follow-up, with a loss to follow-up rate of 22.0%(51/232). Among them, 62 cases(62 eyes)belonged to the 0.01% atropine eye drops group, 54 cases(54 eyes)belonged to the 0.05% atropine eye drops group, and 65 cases(65 eyes)belonged to the control group. There was no significant difference in baseline PD and IOP among the three groups(all P<0.05). After 12 mo of medication, the changes in PD among the 0.01% atropine eye drops group, 0.05% atropine eye drops group, and control group were 0.79±0.70, 1.29±0.66, and 0.06±0.74 mm, respectively(P<0.001). The change in PD in the 0.05% atropine eye drops group was significantly greater than that in both the 0.01% atropine eye drops group and the control group. Similarly, the change in PD in the 0.01% atropine eye drops group was significantly greater than that in the control group(all P<0.05). After 12 mo of medication, the changes in IOP among the 0.01% atropine eye drops group, 0.05% atropine eye drops group, and control group were -0.70±1.94, -0.22±1.79, and 0.25±2.03 mmHg, respectively(P<0.05). The changes in IOP in the 0.05% atropine eye drops group showed statistically significant difference compared to both the 0.01% atropine eye drops group and the control group(all P>0.05), and the changes in IOP in the 0.01% atropine eye drops group were statistically significant compared to the control group(P<0.05). Multivariate linear regression analysis revealed that baseline refractive error and baseline PD were significant factors influencing the change in PD among children treated with atropine eye drops(β=0.230, 95%CI: 0.005-0.455, SE=0.114, t=2.025, P=0.045; β=-0.562, 95%CI: -0.729--0.396, SE=0.084, t=6.697, P<0.001). Additionally, baseline IOP was significant factor influencing the change in IOP among children in the atropine eye drop groups(β=-0.285, 95%CI: -0.439--0.131, SE=0.078, t=3.662, P<0.001).CONCLUSION: The PD of myopic children increased after using 0.01% and 0.05% atropine eye drops, and the change in PD after using 0.05% atropine eye drops was significantly greater than that of 0.01% atropine eye drops. No risk was found in the use of 0.01% and 0.05% atropine eye drops and elevated IOP.

OBJECTIVE To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample. METHODS The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode. RESULTS There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids. CONCLUSION The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.

Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

ObjectiveTo establish the specific chromatogram and thin layer chromatography（TLC） of Qingxin Lianziyin（QXLZY） benchmark samples， in order to clarify the key quality attributes and provide a reference for the quality evaluation of QXLZY. MethodHigh performance liquid chromatography（HPLC） specific chromatogram of QXLZY benchmark samples was developed by using a YMC Hydrosphere C₁₈ column（4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile（A）-0.2% formic acid aqueous solution（B） for gradient elution（0-10 min， 5%-20%A； 10-20 min， 20%A； 20-25 min， 20%-24%A； 25-40 min， 24%-30%A； 40-55 min， 30%-50%A； 55-65 min， 50%-100%A； 65-75 min， 100%A； 75-75.1 min， 100%-5%A； 75.1-90 min， 5%A）， and the detection wavelength was 360 nm. Ultra-high performance liquid chromatography-linear ion trap/orbitrap mass spectrometry（UHPLC-LTQ-Orbitrap MS） with electrospray ionization（ESI） was used to identify the components of QXLZY benchmark samples by accurate relative molecular weight and multilevel MS fragment ion information， the detection conditions were positive and negative ion modes and data dependency scanning mode. TLC identification methods for Ophiopogonis Radix， Lycii Cortex， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma in QXLZY were established. ResultA total of 15 characteristic peaks were identified from Glycyrrhizae Radix et Rhizoma， Plantaginis Semen and Scutellariae Radix， and the relative standard deviations of the retention times of 15 characteristic peaks in 15 batches of QXLZY benchmark samples were≤3% with peak 8（baicalin） as the reference peak. A total of 100 compounds， including flavonoids， organic acids， saponins， amino acids and others， were identified in the benchmark samples by UHPLC-LTQ-Orbitrap MS. The established TLC had good separation and was suitable for the identification of Ophiopogonis Radix， Lycii Cortex， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma in QXLZY. ConclusionThe material basis of QXLZY benchmark samples is basically determined by MS designation and source attribution. The established specific chromatogram and TLC of QXLZY are simple， stable and reproducible， which can provide a reference for the development and quality control of QXLZY.

ObjectiveTo establish the specific chromatogram and thin layer chromatography（TLC） identification method of Kaixinsan（KXS） samples， in order to clarify the key quality attributes and provide reference for the quality evaluation of KXS. MethodHigh performance liquid chromatography（HPLC） specific chromatogram of KXS was developed with YMC Hydrosphere C₁₈ column（4.6 mm×250 mm， 5 μm）， the mobile phase was acetonitrile（A）-0.2% formic acid aqueous solution（B） for gradient elution（0-15 min， 2%-20%A； 15-25 min， 20%-25%A； 25-30 min， 25%-30%A； 30-45 min， 30%-31%A； 45-50 min， 31%-44%A； 50-65 min， 44%-45%A； 65-73 min， 45%-75%A； 73-95 min， 75%-100%A； 95-105 min， 100%A； 105-105.1 min， 100%-2%A； 105.1-120 min， 2%A）， the detection wavelength was 320 nm. Ultra high performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UHPLC-LTQ-Orbitrap MS） was used to identify the chemical components of KXS with electrospray ionization（ESI）， negative ion mode and scanning range of m/z 50-2 000. TLC identification methods for Poria and Ginseng Radix et Rhizoma in KXS were established. ResultThere were 11 common peaks in the specific chromatogram of KXS， attributed to Polygalae Radix， Poria and Acori Tatarinowii Rhizoma. Taking peak 9（α-asarone） as the reference peak， the relative standard deviations of the retention times of 15 batches of KXS samples were<0.2%. A total of 34 compounds were identified by UHPLC-LTQ-Orbitrap MS， including terpenoids， phenylpropanoids， oligosaccharides and ketones. The established TLC had good separation and was rapid， reliable， simple， feasible， suitable for the identification of Poria and Ginseng Radix et Rhizoma in KXS. ConclusionThe specific chromatogram and TLC of KXS are stable and reproducible. The material basis of KXS is basically clarified by MS， which can provide a reference for the development and quality control of KXS.

Hydrogels/therapeutic use* ; Tissue Engineering ; Gelatin ; Intervertebral Disc/surgery* ; Methacrylates ; Tissue Scaffolds

ObjectiveAlmond， which is bitter in taste， contains traces of toxic substances. For the sake of the safety of prescriptions containing this medicinal material， the processing method of "soaking in boiling water" was selected. Moreover， through literature research and network pharmacology， the characteristic index of this medicinal material was determined. On this basis， a method was established for the determination of amygdalin in Qingfei Paidu Granules （QFPD） and the transfer rate of it in the processing of this prescription was monitored， aiming at improving the quality control system of QFPD. MethodThe high performance liquid chromatography conditions are as follows： YMC Triart C₁₈ column （4.6 mm × 150 mm， 5 µm）， mobile phase of methanol-water with flow of 1.0 mL·min^-1， column temperature of 35 ℃， and detection wavelength of 210 nm. ResultThe linear curve fitted well and the average recovery of amygdalin was 97.74% with RSD of 4.3%. The transfer rates of amygdalin from the medicinal material to the extract， from extract to concentrate， and from concentrate to granules were investigated with this method. The result showed that the average transfer rate from the medicinal material to the granules was （60±3.91）%. The comparison of transfer rate between the processes suggesting that the extraction of the medicinal material might be the key part influencing the prescription preparation. ConclusionThe method is simple， sensitive， reproducible， stable， and accurate， and the index is reasonable. Thus， the method can be used for the quality control of QFPD and determination of transfer rate of components in the preparation of QFPD. This study further improves the quality control standard of almond in QFPD， which can serve as a reference for the clinical application of QFPD.

Germany owns the largest herbal market in Europe and has the world's leading R&D capabilities for herbal medicine products. Chinese herbal medicine (CHM) spreaded to Germany hundreds of years ago. Since the beginning of the 20th century, China and Germany have signed a series of agreements to support traditional medicine cooperation, and the exchange of herbs between China and Germany has become more frequent, bringing opportunities for CHM to enter into Germany. In recent years, China and Germany have gained progress in the fields of CHM research and trade, etc. However, there are differences in the understanding of herbal medicines, quality standard evaluation, usage, and medication rules between the two countries. By doing SWOT analysis of the development of CHM in Germany, this paper suggested to promote Sino-German medical exchanges and build a community of common health for mankind through strengthening the clinical application of CHM, finding new ways of CHM entering into German market, and building an international talent team of traditional Chinese medicine.