1.Study on the Quality Evaluation of Shuanghuanglian Oral Liquid after Mutual Substitution of Honeysuckle and Wild Honeysuckle Based on Supramolecular"Imprinting Template"
Haiying LI ; Wenjiao LI ; Ru QIAO ; Fan CHEN ; Xiangting GAO ; Xiao XUE ; Linjuan LIU ; Meifeng XIAO ; Peng HE ; Fuyuan HE
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):120-127
Objective To evaluate the quality of Shuanghuanglian Oral Liquid after mutual substitution of honeysuckle and wild honeysuckle using total quantum statistical moment(TQSM)and molecular connectivity index(MCI).Methods UPLC fingerprint of Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian oral liquid(wild honeysuckle)were established,the TQSM parameters and similarity of the fingerprint were calculated;by reviewing relevant literature,as well as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),chemical composition databases for Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was established,all components were divided into different component groups,and MCI and its similarity were calculated.Results The number of chromatographic peaks and total zero order moment(AUCT)of 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)were higher than those of Shuanghuanglian Oral Liquid(wild honeysuckle),but there was no significant difference in total first order moment(MRTT)and total second order moment(VRTT);the total quantum statistical moment similarity(TQSMS)between 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)was 1.000 0-0.824 6,the TQSMS between 15 batches of Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.659 0,and the TQSMS between 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.619 8.The MCI similarity of various components between Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.984 9,with an overall MCI similarity of 0.995 8.Conclusion There is no significant difference in the various components and overall"imprinting template"between Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle).It is speculated that the substitution of honeysuckle and wild honeysuckle will not affect the pharmacological properties of Shuanghuanglian Oral Liquid,but there may be differences in the intensity of pharmacological effects,with Shuanghuanglian Oral Liquid(honeysuckle)being the most effective.
2.Effect of tongue pressure resistance feedback training on rehabilitation of swallowing disorders in patients with ischemic stroke
Yuan HE ; Weiwei JIA ; Haiying WANG ; Qian ZHANG ; Bing WEI
Journal of Clinical Medicine in Practice 2025;29(8):102-107
Objective To explore the effect of tongue pressure resistance feedback training in the rehabilitation of dysphagia in patients with ischemic stroke(IS).Methods A total of 100 pa-tients with dysphagia after IS were randomly divided into control group(receiving conventional reha-bilitation therapy and oral motor training)and experimental group(receiving tongue pressure resist-ance feedback training on the basis of conventional rehabilitation therapy),with 50 patients in each group.The treatment duration was 4 weeks for both groups.During the study,3 patients dropped out due to personal reasons,and ultimately 49 patients in the control group and 48 patients in the experi-mental group completed the study.Before and after treatment,tongue muscle function was measured in both groups;videofluoroscopic swallowing studies(VFSS)were used to measure temporal and kinemat-ic parameters of swallowing;the Rosenbek Penetration-Aspiration Scale(PAS)was used to assess aspi-ration risk;the Stroke and Aphasia Quality of Life Scale(SWAL-QOL)was used to evaluate quality of life;and occurrence of complications in both groups were compared.Results After 4 weeks of treat-ment,peak tongue pressure,mean tongue pressure,and tongue pressure duration increased inboth groups,with these indicators being higher in the experimental group than in the control group;oral transit time,soft palate elevation time,and hyoid bone displacement time shortened,while upper esoph-ageal sphincter(UES)opening time and laryngeal closure time prolonged,hyoid and thyroid cartilage movement(upward and anterior displacement)and UES opening degree increased,and pharyngeal contractile ratio(PCR)decreased in both groups,with these indicators being superior in the experi-mental group compared to the control group;PAS scores decreased and SWAL-QOL scores increased in both groups,with PAS scores being lower and SWAL-QOL scores being higher in the experimental group compared to the control group;the differences between the two groups in the aforementioned indicators were statistically significant(P<0.05).The complication rate was 4.17%(2/48)in the experimental group and 10.20%(5/49)in the control group,with no statistically significant difference(P>0.05).Conclusion Tongue pressure resistance feedback training can improve tongue function and swallowing function,effectively reduce the risk of aspiration after swallowing,and enhance the quality of life of patients with dysphagia after IS during their rehabilitation treatment.
3.The Establishment of a Virus-related Lymphoma Risk Warning System and Health Management Model Based on Traditional Chinese Medicine Conditions
Hanjing LI ; Shunan LI ; Zewei ZHUO ; Shunyong WANG ; Qiangqiang ZHENG ; Bingyu HUANG ; Yupeng YANG ; Chenxi QIU ; Ningning CHEN ; He WANG ; Tingbo LIU ; Haiying FU
Journal of Traditional Chinese Medicine 2025;66(4):335-339
Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease, making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine (TCM) in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation, using standardized measurements of the overall TCM condition, multi-omics research of hematologic tumors, and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma, thereby establishing a risk warning system for virus-related lymphoma. At the same time, a TCM health management approach will be applied to manage and regulate virus-related lymphoma, interrupting its progression and forming a human-centered, comprehensive, continuous health service model. Based on this, a standardized, integrated clinical prevention and treatment decision-making model for virus-related lymphoma, recognized by both Chinese and western medicine, will be established to provide TCM solutions for primary prevention of major malignant tumors.
4.Study on the distribution of traditional Chinese medicine syndromes and syndrome elements in lymphoma and the correlation between syndromes and Western medicine clinical indicators
Hanjing LI ; Shunan LI ; Zewei ZHUO ; Shunyong WANG ; Qiangqiang ZHENG ; Bingyu HUANG ; Yupeng YANG ; Chenxi QIU ; Ningning CHEN ; Yanyan QIU ; He WANG ; Tingbo LIU ; Haiying FU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):127-137
Objective:
To investigate the distribution of traditional Chinese medicine (TCM) syndromes and syndrome elements in lymphoma, as well as the correlation between TCM syndromes and Western clinical indicators, in order to analyze associations between TCM syndromes and these indicators.
Methods:
From January 2023 to May 2024, 216 patients with lymphoma who met the inclusion criteria in the Department of Hematology, Third People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were enrolled. Four diagnostic methods were applied to perform TCM syndrome differentiation and extract syndrome elements. The correlations between various syndromes and blood test indicators of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), white blood cell (WBC), hemoglobin (Hb), platelet count (PLT), neutrophil (NEUT), immunohistochemical markers of B-cell lymphoma-6 (BCL6), B-cell lymphoma-2 (BCL2), proto-oncogene MYC, and Ki67 protein expression, Ann Arbor staging, international prognostic index (IPI) score, bone marrow infiltration, concurrent infections during chemotherapy, and post-chemotherapy bone marrow suppression rate were analyzed.
Results:
Five TCM syndromes, ranked by frequency, were syndromes of yin deficiency with phlegm accumulation(41.67%), qi depression with phlegm obstruction(30.56%), cold-phlegm congelation and stagnation(12.96%), phlegm-blood stasis toxin(12.04%), and lingering pathogen due to deficient vital qi(2.77%). Yin deficiency(50.93%) and phlegm(45.37%) were the more prevalent syndrome elements. The TCM syndromes were correlated with β2-MG, PLT, MYC, BCL2/MYC, Ki67 protein expression, and bone marrow infiltration (P<0.05). No statistically significant differences were observed in Ann Arbor staging or IPI score across the syndromes. Compared to the syndrome of cold-phlegm congelation and stagnation, the syndrome of qi depression with phlegm obstruction exhibited higher levels of NEUT, MYC, BCL2/MYC, and Ki67 protein expression, as well as a higher rate of post-chemotherapy bone marrow suppression (P<0.05); the syndrome of phlegm-blood stasis toxin showed higher MYC and BCL2/MYC protein expression and a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05); the syndrome of yin deficiency with phlegm accumulation demonstrated higher MYC and BCL2/MYC protein expression and bone marrow infiltration rates, whereas PLT level was lower (P<0.05); the syndrome of lingering pathogen due to deficient vital qi had higher MYC, BCL2/MYC, and Ki67 protein expression levels, as well as a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05). Compared to the syndrome of qi depression with phlegm obstruction, the syndrome of phlegm-blood stasis toxin exhibited lower Ki67 protein expression (P<0.05); the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, bone marrow infiltration rate, and rate of concurrent infections during chemotherapy, whereas PLT and NEUT levels and the rate of post-chemotherapy bone marrow suppression rate were lower (P<0.05). Compared to the syndrome of phlegm-blood stasis toxin, the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, whereas NEUT and the rate of post-chemotherapy bone marrow suppression were lower(P<0.05); the syndrome of lingering pathogen due to deficient vital qi exhibited a higher Ki67 protein expression (P<0.05). Compared to the syndrome of yin deficiency with phlegm accumulation, the syndrome of lingering pathogen due to deficient vital qi also showed a higher Ki67 protein expression(P<0.05).
Conclusion
The syndrome of yin deficiency with phlegm accumulation is relatively common in lymphoma. There is a correlation between TCM syndromes and Western medicine clinical indicators. The presence of heat signs in the syndromes may indicate active disease and poor prognosis, while the presence of strong pathogenic factors and weak vital qi in the syndromes may indicate a severer chemotherapy-related bone marrow suppression.
5.Optimization of Processing Technology of Calcined Pyritum Based on QbD Concept and Its XRD Fingerprint Analysis
Xin CHEN ; Jingwei ZHOU ; Haiying GOU ; Lei ZHONG ; Tianxing HE ; Wenbo FEI ; Jialiang ZOU ; Yue YANG ; Dewen ZENG ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):197-205
ObjectiveBased on the concept of quality by design(QbD), the processing process of calcined Pyritum was optimized, and its X-ray diffraction(XRD) fingerprint was established. MethodsThe safety, effectiveness and quality controllability of calcined Pyritum were taken as the quality profile(QTPP), the color, hardness, metallic luster, phase composition, the contents of heavy metals and hazardous elements were taken as the critical quality attributes(CQAs), and the calcination temperature, calcination time, paving thickness and particle size were determined as the critical process parameters(CPPs). Differential thermal analysis, X-ray diffraction(XRD) and inductively coupled plasma mass spectrometry(ICP-MS) were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then, based on the criteria importance through intercriteria correlation(CRITIC)-entropy weight method, the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process, and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures, and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS2 to Fe7S8 during the process of temperature increase, the color gradually deepened from dark yellow, and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows:calcination temperature at 750 ℃, calcination time of 2.5 h, paving thickness of 3 cm, particle size of 0.8-1.2 cm, vinegar quenching 1 time[Pyritum-vinegar(10∶3)]. After calcination, the internal structure of Pyritum was honeycomb-shaped, which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96, and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing, the dissolution of the effective components in Pyritum increases, and the contents of heavy metals and harmful substances decrease, reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible, and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.
6.Optimization of Processing Technology of Calcined Pyritum Based on QbD Concept and Its XRD Fingerprint Analysis
Xin CHEN ; Jingwei ZHOU ; Haiying GOU ; Lei ZHONG ; Tianxing HE ; Wenbo FEI ; Jialiang ZOU ; Yue YANG ; Dewen ZENG ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):197-205
ObjectiveBased on the concept of quality by design(QbD), the processing process of calcined Pyritum was optimized, and its X-ray diffraction(XRD) fingerprint was established. MethodsThe safety, effectiveness and quality controllability of calcined Pyritum were taken as the quality profile(QTPP), the color, hardness, metallic luster, phase composition, the contents of heavy metals and hazardous elements were taken as the critical quality attributes(CQAs), and the calcination temperature, calcination time, paving thickness and particle size were determined as the critical process parameters(CPPs). Differential thermal analysis, X-ray diffraction(XRD) and inductively coupled plasma mass spectrometry(ICP-MS) were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then, based on the criteria importance through intercriteria correlation(CRITIC)-entropy weight method, the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process, and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures, and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS2 to Fe7S8 during the process of temperature increase, the color gradually deepened from dark yellow, and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows:calcination temperature at 750 ℃, calcination time of 2.5 h, paving thickness of 3 cm, particle size of 0.8-1.2 cm, vinegar quenching 1 time[Pyritum-vinegar(10∶3)]. After calcination, the internal structure of Pyritum was honeycomb-shaped, which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96, and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing, the dissolution of the effective components in Pyritum increases, and the contents of heavy metals and harmful substances decrease, reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible, and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.
7.Inhibition of the cGAS‑STING Pathway Reduces Cisplatin-Induced Inner Ear Hair Cell Damage.
Ying SUN ; Shengyu ZOU ; Xiaoxiang XU ; Shan XU ; Haiying SUN ; Mingliang TANG ; Weijia KONG ; Xiong CHEN ; Zuhong HE
Neuroscience Bulletin 2025;41(3):359-373
Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity*
;
Animals
;
Nucleotidyltransferases/antagonists & inhibitors*
;
Membrane Proteins/antagonists & inhibitors*
;
Signal Transduction/drug effects*
;
Mice
;
Hair Cells, Auditory, Inner/pathology*
;
Antineoplastic Agents/toxicity*
;
Mice, Inbred C57BL
;
Hearing Loss/metabolism*
;
Male
;
Ototoxicity/metabolism*
8.Mechanisms of sufentanil on alleviating sepsis-induced myocardial injury through activating AMPK/Nrf2/HO-1 pathways,mediating oxidative stress and inhibiting ferroptosis
Xuan XIANG ; Wen MENG ; Junjin CHEN ; Fanghong CHEN ; Haiying LI ; Xueming HE
Chinese Journal of Nosocomiology 2025;35(10):1460-1465
OBJECTIVE To study the mechanisms and effect of sufentanil(SUF)on protection of sepsis-induced myocardial injury.METHODS The in vitro experimental models of sepsis-induced myocardial injury were estab-lished by using lipopolysaccharide(LPS).The myocardial H9C2 cells were divided into the Control group,the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group;the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group were the experimental groups.The cells from the experimental groups were respec-tively inoculated and incubated in culture media containing 25 mg/L of LPS,and the culture media were respec-tively added SUF with the terminal dose of 0,5,10,20,20 and 20 μmol/L;the culture media of the SUF-H-ComC was added ComC with the terminal dose of 10 μmol/L,and the culture media of the SUF-H-ML385 was added ML385 with the terminal dose of 5 μmol/L.The cells from the Control group were incubated in normal cul-ture media.The same amount of culture media and CCK-8 reagent without containing myocardial H9C2 cells were assigned as the blank group.The cell viability was determined by CCK-8 method,the levels of reactive oxygen species(ROS),malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)were detected.The Fe2+level of the cells was detected by iron ion colorimetric meth-od.The levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in supernatant fluid of the culture media were detected with the use of enzyme-linked immunosorbent assay.The expression levels of adenosine 5'-monophosphate-activated protein kinas(AMPK),phosphorylated-AMPK(p-AMPK),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by means of Western Blot.RESULTS The cell viability of the LPS group was lower than that of the Control group;the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α of the LPS group were higher than those of the Control group;the levels of SOD and GSH-Px of the LPS group were lower than those of the Control group;the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins of the LPS group were lower than those of the Control group(P<0.05).As compared with the LPS group,the cell viability of the SUF-L group,the SUF-M group and the SUF-H group was succes-sively increased,the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α were successively reduced,the levels of SOD and GSH-Px were successively elevated,and the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins were successively increased(P<0.05).AMPK pathway inhibitor and Nrf2 pathway inhibitor could reverse the viability of SUF-affecting LPS-induced myocardial H9C2 cells,levels of ROS,MDA,LDH,Fe2+,SOD,GSH-Px,IL-1β,IL-6 and TNF-α and downregulated the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins(P<0.05).CONCLUSION SUF can improve the sepsis-induced myocardial injury,and the mecha-nism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways,inhibition of ferroptosis,oxi-dative stress injury and inflammatory reactions.
9.Establishment and systematic evaluation of a mouse model of chronic obstructive pulmonary disease induced by cigarette smoke
Haiying ZHANG ; Xiao YU ; Menghui HOU ; Nan WANG ; Chang ZHANG ; Qianhui MA ; Minghe LI ; Xu HE
Acta Laboratorium Animalis Scientia Sinica 2025;33(10):1439-1447
Objective To establish and evaluate a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS).Methods Forty BALB/c mice were divided randomly into a control group and a CS group.Mice in the CS group were subjected to passive smoking for 20 weeks and a COPD model was established.Morphological changes in the organs and lung,heart,liver,and kidney fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Lung,cardiac,and brain cognitive function were evaluated by pulmonary function testing,small-animal ultrasound,and Morris water maze trials.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1β levels in lung and brain tissues were detected by ELISA.Liver and renal functions were measured by biochemical method.Results The alveolar septum was narrowed or broken in mice in the CS group,and the adjacent alveolar cavity was enlarged and fused,consistent with the pathological changes of COPD.Neuronal degeneration and necrosis were observed in the hippocampus,but there were no significant morphological changes in other organs.Masson staining showed no obvious fibrosis in the lung,heart,liver,or kidney in CS-group mice.The result of pulmonary function tests showed that the forced expiratory volume in 0.1 second/forced vital capacity(FEV 0.1/FVC)and dynamic compliance were significantly decreased in the CS group compared with the control group,while airway resistance was obviously increased.Cognitive impairment in mice in the CS group was confirmed in the Morris water maze trial.TNF-α,IL-6,and IL-1β levels in lung and brain tissues were higher in the CS group compared with the control group.There were no significant differences in cardiac,liver,and renal functions between the groups.Conclusions A mouse model of COPD can be established by CS exposure for 20 weeks.Lung histomorphology,lung function,brain cognitive function,and levels of inflammatory factors can be used as indicators to evaluate the success of the model.
10.Genetic and phenotypic analysis of Hermansky-Pudlak syndrome type 6 family with a special platelet phenotype
Zhongqiang ZHOU ; Pingling SHI ; Haiying PENG ; Qian LI ; He TANG ; Yuanmeng WEI
Chinese Journal of Ocular Fundus Diseases 2025;41(9):690-696
Objective:To identify and observe the pathogenic genes and clinical phenotypes of a family with a special platelet phenotype, Hermansky-Pudlak syndrome type 6 (HSP6).Methods:A retrospective clinical study. In November 2019, one proband and three family members from six HSP families who visited Henan Eye Hospital were included in the study. The child's medical history and family history were inquired in detail. The proband and all family members underwent best corrected visual acuity (BCVA), fundus color photography, frequency-domain optical coherence tomography, and general physical examination. The proband underwent platelet transmission electron microscopy (PTEM) and colonoscopy. Peripheral venous blood was collected from the proband, her parents and younger brother, and genomic DNA was extracted. Whole exome sequencing (WES) was used to screen pathogenic genes and their loci. Bioinformatics analysis determines the pathogenicity of gene variation sites. Fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to verify the related variations.Results:The proband (Ⅱ-1) was a 7-year-old female. The BCVA in both eyes was 0.1, who exhibited mild horizontal nystagmus and iris depigmentation. Fundus examination revealed obvious depigmentation and an underdeveloped fovea centralis. At the age of 7, the patient underwent colonoscopy due to acute gastrointestinal bleeding. A polyp approximately 5 mm in size was found on the floor of the sigmoid colon, with erosion and mucosal leukoplakia on its surface. PTEM showed that the number of platelet dense granules was normal, but the nuclei were small or exhibited low compactness. The skin on both lower legs showed pigmentation. The clinical phenotypes of the proband’s parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) showed no obvious abnormalities. WES revealed that the proband carried compound heterozygous variants in exon 1 of the HPS6 gene: c.60_64dup (p.L22fs) (M1) and c.1147_1148del (p.L383fs) (M2). The mother carried the M1 variant, while the father and younger brother carried the M2 variant. Bioinformatics analysis predicted that both variants were pathogenic. RT-qPCR results showed that, compared with the relative expression level of HPS6 wt mRNA, the relative expression levels of HPS6 L22fs and HPS6 L383fs mRNA were significantly decreased ( t = 3.549, 4.560; P<0.05). Western blot analysis demonstrated that the HPS6 L383fs protein was truncated, whereas the HPS6 L22fs protein was not detected. Conclusions:This family is a special HPS6 with a normal number of dense platelet granules. The compound heterozygous variations of M1 and M2 in the HPS6 gene are pathogenic genes in this family.


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