OBJECTIVE: To develop a quality consistency evaluation strategy for traditional Chinese medicine (TCM) granules using sugar free Yangwei Granules as a model drug, and demonstrate the effectiveness of the developed method. METHODS: The strategy integrates several methods including, HPLC fingerprint and physical fingerprint methods analyze the similarity in chemical and physical properties of the TCM granule samples. Near-infrared (NIR) spectroscopy with principal components cluster analysis method is used to monitor normal operating conditions (NOC) samples accurately and to identify different types of abnormal operating conditions (AOC) samples, particularly those that deviate from the normal range. RESULTS: The combined use of HPLC fingerprint and physical fingerprint provides insights into the chemical and physical properties of the samples. NIR spectroscopy, combined with principal components cluster analysis, achieves high accuracy in monitoring NOC samples and identifying AOC samples without misjudgment. The approach proves useful as a complementary method in cases where HPLC fingerprint and physical fingerprint alone lack sufficient resolution. CONCLUSION This study establishes the feasibility and utility of the integrated approach for assessing the quality consistency of TCM granules. The strategy shows a high degree of generalization and holds significant importance for enhancing the quality control processes of TCM granules.

Objective To summarize the medication law of TCM in the treatment of chronic bronchitis;To provide reference for clinical medication.Methods Medical records of patients with chronic bronchitis who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 1,2016 to December 31,2021 were extracted based on HIS electronic medical record data.After screening,the TCM prescriptions used by patients with chronic bronchitis were input into Excel 2019 to establish a database.Based on the software Lantern 5.0,the latent structure model was learned,hidden variables and explicit variables were obtained,and the model was interpreted.SPSS Modeler 18.0 was used to establish model points with Apriori algorithm for Chinese materia medica with a frequency greater than 6%,to obtain the association rules between drugs,and to analyze the medication law of TCM in treating chronic bronchitis.Results A total of 3 410 cases were included,involving 423 kinds of Chinese materia medica,with a cumulative frequency of 82 766 times.Among them,109 kinds of Chinese materia medica with a frequency of>6 % had a cumulative frequency of 69 845 times.The top five commonly used medicines were Fritillariae Cirrhosae Bulbus,Poria,Atractyodis Macrocephalae Rhizoma,Asteris Radix et Rhizoma,Citri Reticulatae Pericarpium,mainly with medicines of reducing cough and phlegm,antiasthmatic medicine,tonifying deficiency,clearing heat,relieving superficies,promoting blood circulation and removing blood stasis.The medicinal properties were warming,cold and mild,and the main tastes were bitter,sweet and pungent,and the meridians were mainly lung,spleen,liver and stomach meridians.Through analysis of latent structure,49 hidden variables and 149 hidden classes were obtained.Combined with professional knowledge,10 comprehensive clustering models and 21 core formulas were deduced,such as Sangbaipi Decoction,Xuefu Zhuyu Decoction,Xiaoqinglong Decoction,Erchen Decoction,Shashen Maidong Decoction,Liuwei Dihuang Pills,Yinqiao Powder,Zhisou Powder,Yupingfeng Powder,Xuefu Zhuyu Decoction combined with Daotan Decoction,etc.It was concluded that the chronic bronchitis syndrome included phlegm-heat stagnation lung syndrome,qi stagnation blood stasis syndrome,cold fluid attacking lung syndrome,phlegm-dampness accumulation lung syndrome,lung qi and yin deficiency syndrome,kidney yin deficiency syndrome,wind heat attacking lung syndrome,wind cold attacking lung syndrome,lung qi and spleen deficiency syndrome,phlegm stasis interjunction syndrome.A total of 41 strong association rules were screened in the analysis of association rules,including 5 strong association rules for two and 36 strong association rules for three.The high confidence rules were Saposheikovize Radix + Angelicae Sinensis Radix →Atractyodis Macrocephalae Rhizoma,Saposheikovize Radix + Codonopsis Radix → Atractyodis Macrocephalae Rhizoma,Codonopsis Radix + Citri Reticulatae Pericarpium → Atractyodis Macrocephalae Rhizoma;the higher degree of improvement were Bupleuri Radix + Mori Cortex → Scutellariae Radix,Perillae Fructus + Belamcandae Rhizoma → Fritillariae Cirrhosae Bulbus,Armeniacae Semen Amarum + Pinelliae Rhizoma → Citri Reticulatae Pericarpium,etc.Conclusion In the treatment of chronic bronchitis,TCM is mainly used to reduce phlegm,relieve cough and asthma,and the method of promoting blood circulation and removing blood stasis is commonly used to help eliminate phlegm.In addition,TCM pays attention to the application of methods such as tonifying lung and securing the exterior,invigorating spleen and benefiting qi.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

OBJECTIVE: To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease. METHODS: Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis. RESULTS: Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3). CONCLUSION The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.
Dyneins/genetics* ; Genomics ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Sperm Tail/pathology* ; Whole Exome Sequencing

The industry of traditional Chinese medicine (TCM) encounters problems like quality fluctuation of raw materials and unstandardized production process. Near infrared (NIR) spectroscopy technology is widely used in quality control of TCM because of its abundant information, fast and nondestructive characters. The main applications include quantitative analysis of Chinese medicinal materials, intermediates and Chinese patent medicines; the authenticity of TCM, species, origins and manufacturers; monitoring and control of the extraction, alcohol precipitation, column chromatography and blending process. This article reviews the progress on the application of NIR spectroscopy technology in TCM field. In view of the problems existing in the application, the article proposes that the standardization of NIR analysis method should be developed according to specific characteristics of TCM, which will promote the application of NIR technology in the TCM industry.
Drugs, Chinese Herbal ; standards ; Medicine, Chinese Traditional ; methods ; standards ; Pharmaceutical Preparations ; standards ; Quality Control ; Spectroscopy, Near-Infrared ; methods ; standards

It has been widely accepted in modern pharmaceutical industry that quality cannot be tested into products , instead quality should be built-in by design . However , the implementation of Quality by Design ( QbD ) in development , manufacture and supervision of traditional Chinese medicine ( TCM ) still remains to be a challenge . The program of safety re-evaluation of TCM injections provides an opportunity to practice QbD approach in TCM industry . This paper discussed some potential ways that improve the quality of TCM injec-tions base on QbD related tools , including identification of critical quality attributes , critical process parameters and critical material attributes, development of design space and control strategy.

OBJECTIVETo suggest a method for discriminating quality control indicators of concentrated solution before traditional Chinese medicine ethanol precipitation.

METHODThe second ethanol precipitation (SEP) of Guanxinning was taken as an example, with the concentrated supernatant of first ethanol precipitation (CSFEP) prepared with same dry matter content and the same amount of ethanol as raw materials, to conduct the ethanol precipitation test under the same conditions. The experimental data was analyzed by stepwise regression and partial least squares regression. Both of them selected the parameters which affect phenolic compounds retention ratios in SEP supernatant as the key indicators.

RESULTPhenolic compounds contents in SEP supernatant were mainly affected by the contents of danshensu, caffeic acid and salvianolic acid B in CSFEP.

CONCLUSIONThe discrimination method can be used to discover key quality control indicators of concentrated solution before ethanol precipitation.

Chemical Precipitation ; Ethanol ; chemistry ; Medicine, Chinese Traditional ; standards ; Quality Control ; Solutions

OBJECTIVETo establish a method for monitoring the quality of intermediates generated in each working procedure during the production process of traditional Chinese medicine (TCM) , in order to ensure the batch-to-batch quality consistency of TCM products.

METHODThe multistage multivariate statistic quality control (MMSQC) was proposed to monitor production quality of TCMs based on multivariate data analysis technique. Hotelling T2 and SPE were adopted for monitoring the quality of intermediates generated in each working procedure. Danshen injection was taken as the example to introduce the application method of MMSQC.

RESULTMMSQC can monitor the quality of intermediates generated in multiple working procedures, which is simpler and more accurate compared with single-indicator monitoring method.

CONCLUSIONMMSQC can be popularized to monitor quality of multistage production of TCMs.

Drugs, Chinese Herbal ; chemistry ; standards ; Medicine, Chinese Traditional ; standards ; Phenanthrolines ; chemistry ; standards ; Quality Control ; Salvia miltiorrhiza ; chemistry

OBJECTIVEWater content in concentrated extract (WCCE), the concentration of ethanol used in precipitation (CEA) and the quantity of ethanol added( QEA) are three important variables in the first ethanol precipitation of Danshen injection. In this work, the relationships between the three variables and total solid removal, Danshensu (DSS)retention and DSS purity were investigated.

METHODExperiments according to central composite design were carried out and mathematical models were developed.

RESULTThe models were accurate and predictive. The relative deviations between prediction results and experimental results were less than 3%. The influences of the three variables were discussed with a response surface method. The decrease of WCCE and the increase of CEA both caused more precipitation and increase the purity of DSS. However, more loss of DSS was observed. The increase of QEA increased total solid removal. DSS retention and DSS purity increased first and then decreased when QEA increased.

CONCLUSIONThis result suggests the addition of ethanol should be optimized according to WCCE and CEA to obtain better supernatant

Chemical Precipitation ; Ethanol ; chemistry ; Models, Statistical ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry ; Water ; chemistry

OBJECTIVEA component-knockout approach was established to discover active components from traditional Chinese medicine.

METHODAccording to the principle of gene knockout technique, an experiment workflow for component-knockout method was developed, which is distinct from the bio-guided screening method. The differences of therapeutic efficacies between different combinations of individual components were analyzed by some statistical methods including Analysis of Variance (ANOVA), whilst a set of criterias were established to assess active components. By comparing the difference of drug efficacy between the original formulae and the mixture being knockout certain component, the active components can be identified.

RESULTThe presented component-knockout method was applied to discover the active components of Shenmai formulae for the synergistic effects on the cyclophosphamide chemotherapy for S180 tumor-bearing mice. The results indicated that panoxadiol, a type of ginsenosides, were the effective components of Shenmai formulae.

CONCLUSIONA new method for identifying effective components from Chinese medicinal formulae was developed and successfully applied to discover the active components of Shenmai Formulae, which possesses the synergistic actions towards chemotherapy process.

Algorithms ; Analysis of Variance ; Animals ; Diagnosis, Differential ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Gene Knockout Techniques ; Ginsenosides ; chemistry ; therapeutic use ; Medicine, Chinese Traditional ; Mice ; Phytotherapy ; Spectrometry, Mass, Electrospray Ionization