1.Huashi Baidu Granules Treat Influenza Viral Pneumonia by Regulating Gut-Lung Axis
Qijing LI ; Hanhui HUANG ; Yurong DENG ; Ao'ao WANG ; Jianliang LI ; Jianhui SUN ; Liyu HAO ; Zongyuan LI ; Guimin LIU ; Hongmei LI ; Luqi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(23):59-69
ObjectiveTo explore the mechanism of Huashi Baidu granules in treating influenza A (H1N1) virus infection based on the gut-lung axis. MethodsBALB/c mice were randomly assigned into a blank control group, a model control group, a positive control (oseltamivir phosphate capsules, 19.5 mg·kg-1) group, and a Huashi Baidu granules (17.81 g·kg-1) group. Mice in other groups except the blank control group were instilled nasally by H1N1 viral fluid for the modeling of influenza viral pneumonia and treated with corresponding drugs once daily by gavage for 5 consecutive days. The mouse lung index was calculated, and pathological changes in the lung and colon tissue were observed. Western blot was employed to quantify the expression levels of nucleotide-binding oligomeric domain-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteinase -1 (Caspase-1), apoptosis-associated Speck-like protein containing a CARD (ASC), gasdermin D (GSDMD), interleukin-18 (IL-18), IL-1β, and colonic tight junction protein 1 (CLDN1), and Occludin in the lung and colon tissue. Non-targeted metabolomics was employed to analyze the metabolic profiles of the lung tissue and intestinal contents. The 16S rRNA sequencing was performed to analyze the gut microbiota structure in intestinal contents. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the 5-hydroxytryptamine (5-HT) levels in the serum, lung tissue, and colon tissue. ResultsCompared with the blank control group, the model control group showed elevated lung index, marked inflammatory cell infiltration and alveolar structural destruction in the lung tissue, obvious inflammatory cell infiltration and mucosal epithelial damage in the colon tissue, upregulated protein levels of NLRP3 inflammasome pathway proteins NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in the lung and colon tissue (P<0.05, P<0.01), downregulated protein levels of CLDN1 and Occludin in the colon tissue (P<0.05, P<0.01). Compared with the model control group, Huashi Baidu Granules reduced the lung index (P<0.01), alleviated pathological damage in the lungs and colon, inhibited the expression of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in lung and colon tissue (P<0.05, P<0.01), and upregulated the expression of CLDN1 and Occludin in the colon tissue (P<0.05, P<0.01). Metabolomics analysis showed that Huashi Baidu Granules downregulated the 5-HT pathway and arachidonic acid metabolism pathway in the lung and colon tissue, while upregulating nucleotide metabolism and TCA cycle. Compared with the blank control group, the model control group exhibited elevated levels of 5-HT in the serum, lung tissue, and colon tissue (P<0.01). The intervention with Huashi Baidu Granules lowered the levels of 5-HT in the serum (P<0.05) and the lung and colon tissue (P<0.01). Huashi Baidu Granules increased the diversity of gut microbiota, enriched beneficial bacteria such as Blautia, and inhibited pathogenic bacteria such as Desulfovibrio. ConclusionHuashi Baidu Granules significantly alleviate lung inflammation and pathological damage in mice infected with influenza A (H1N1) virus, reshape the intestinal microecology, and repair the intestinal barrier. It may exert cross-organ regulation by inhibiting the cascade of "gutogenic 5-HT release-circulatory transport-pulmonary 5-HT receptor activation-NLRP3 inflammasome assembly." It exerts therapeutic effects on influenza viral pneumonia through the gut-lung axis. This study provides a modern biological interpretation for the TCM theories of interior-exterior relationship between the lung and large intestine and simultaneous treatment of the lung and intestine.
2.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Algorithms
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Lung Diseases/etiology*
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Machine Learning
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Neurosurgical Procedures/adverse effects*
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Postoperative Complications/diagnosis*
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Risk Factors
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ROC Curve
3.Risk factor analysis for postoperative pulmonary infections with multidrug-resistant bacteria in patients with oral squamous cell carcinoma undergoing flap repair surgery
WANG Qian ; PENG Hui ; ZHANG Liyu ; YANG Zongcheng ; WANG Yuqi ; PAN Yu ; ZHOU Yu
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):554-562
Objective:
To investigate the distribution patterns and risk factors for multidrug-resistant bacterial pulmonary infections in patients with oral squamous cell carcinoma (OSCC) undergoing flap reconstruction surgery, and to provide evidence for infection prevention and treatment in this population.
Methods:
This study was approved by the institutional medical ethics committee. We retrospectively analyzed sputum culture results, antimicrobial susceptibility testing data, and clinical records of 109 OSCC patients undergoing flap reconstruction. Chi-square tests were employed to identify pathogens and risk factors for multidrug-resistant bacteria (MDR) in postoperative pulmonary infections. Multivariate logistic regression analysis was conducted to determine MDR risk factors and establish a nomogram prediction model. The model’s discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).
Results:
Among the 109 patients, 52 had negative sputum cultures and 57 tested positive, of whom 14 developed multidrug-resistant (MDR) pulmonary infections. Chi-square analysis revealed that blood transfusion, pre-existing pulmonary diseases, operation time ≥ 490 min, intraoperative blood loss ≥ 400 mL, and abnormal BMI were significant risk factors for postoperative MDR infections (P < 0.05). Multivariate logistic regression identified pre-existing pulmonary diseases, intraoperative blood loss ≥ 400 mL, abnormal BMI, and operative duration ≥ 490 min as independent risk factors for MDR infections (P < 0.05). The nomogram prediction model for MDR infections demonstrated an area under the ROC curve (AUC) of 0.874 (95% CI: 0.775-0.973). The calibration plot showed good agreement between predicted and observed outcomes. DCA indicated a net clinical benefit when the threshold probability for high-risk MDR infections ranged from 0.000 to 0.810. Common MDR pathogens included MDR Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA).
Conclusion
Among OSCC patients undergoing flap reconstruction, MDR pulmonary infections were predominantly caused by gram-negative bacteria (including CRAB, MDR Pseudomonas aeruginosa, and MDR Klebsiella pneumoniae along with the gram-positive pathogen MRSA. Pre-existing pulmonary comorbidities, prolonged surgery duration (≥ 490 min), significant intraoperative blood loss (≥ 400 mL), and abnormal BMI were confirmed as independent risk factors for these MDR infections. The nomogram predictive model incorporating these four variables demonstrated clinically reliable accuracy in risk stratification for postoperative MDR pulmonary infections in this patient population.
4.The changes in retinal and choroidal blood after scleral buckling surgery for rhegmatogenous retinal detachment
Liyu REN ; Xiaoli LI ; Shiyong XIE ; Quanhong HAN ; Ying WANG
Chinese Journal of Ocular Fundus Diseases 2025;41(5):349-357
Objective:To observe the hemodynamic changes in the retina and choroid after scleral buckling surgery in eyes with rhegmatogenous retinal detachment (RRD).Methods:A prospective clinical observational study. A total of 25 eyes of 25 patients with RRD who underwent scleral buckling surgery in Tianjin Eye Hospital from February to April 2024 were included in the study. Among them, 10 were male and 15 were female. Age was 17-68 years old. All cases were monocular. The surgical eye and the contralateral healthy eye were divided into the affected eye group and the contralateral healthy eye group respectively. Best corrected visual acuity (BCVA), scanning source optical coherence tomography angiography (SS-OCTA), and axial length (AL) measurements were performed 3 months after surgery. SS-OCTA examination of macular area was performed by VG200 of Visual Microimaging (Henan) Technology Co., LTD. Scanning range 21 mm×26 mm. According to the partitioning method of the early treatment group of glycosuria retinopathy, the retina within 21 mm of the macular fovea was divided into concentric circles with the macular fovea as the center and diameters of 1-3, 3-6, 6-12, 12-21 mm, respectively. The built-in software of the device was used to record the central area (12 mm×12 mm in the fovea of the macula) and the peripheral area (12-21 mm range) retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), radial peripapillary capillaries (RPC) blood density and choroidal vascular index (CVI), choroidal vascular volume (CVV), and 1-3, 3-6, 6-12, 12-21 mm above concentric circles (S), nasal side (N), temporal side (T), and lower side (I) SCP, DCP, and RPC blood flow density. Quantitative data between the two groups were compared by independent sample t test or Wilcoxon signed rank test. The correlation between retinal and choroid blood flow parameters and postoperative BCVA was analyzed by Spearman correlation analysis. Results:Compared with the opposite healthy eye group, SCP blood density in the central area ( Z=-4.372), DCP blood density in the central area ( Z=-2.829), and CVI in the peripheral area ( Z=-2.138) were decreased in the affected eye group, and the differences were statistically significant ( P<0.05). SCP: in the affected eye group, the blood flow density in T 3-6 mm, T 6-12 mm, N 6-12 mm and T 12-21 mm regions decreased, while the blood flow density in I 6-12 mm regions increased, with statistical significance ( P<0.05). DCP: blood flow density in S 6-12 mm, I 6-12 mm, S 12-21 mm and I 12-21 mm regions decreased significantly, and the differences were statistically significant ( P<0.05). RPC: blood flow density decreased significantly in T 6-12 mm and I 12-21 mm, and the differences were statistically significant ( P<0.05). CVI: T 6-12 mm, S 12-21 mm, T 12-21 mm, I 12-21 mm significantly decreased, and T 1-3 mm, S 12-21 mm significantly increased, the differences were statistically significant ( P<0.05). Correlation analysis showed that AL growth was positively correlated with CVV in central region ( r=0.408, P=0.040). The number of pad pressure was negatively correlated with the blood density of central DCP ( r=-0.422, P=0.030). Conclusions:After scleral buckling operation, the blood flow density and choroidal blood flow parameters in RRD affected eyes are lower than those in contralateral healthy eyes in some areas. The increase of AL is positively correlated with CVV in the central region, and the wider the range of pad pressure, the worse the recovery of DCP blood density.
5.The Scientific Connotation of"Heart and Brain Co-Dominating the Mind"and Its Application in the Treatment of Insomnia by Acupuncture
Yuting ZHANG ; Shan QIN ; Xiaoqiu WANG ; Liyu LIN ; Mufeng LI ; Wenzhong WU ; Chengyong LIU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):181-188
The paper discusses the scientific connotation of"heart and brain co-dominating the mind",including the connotation of"heart and brain co-dominating the mind"in traditional Chinese medicine and the physiological and pathological relationship be-tween heart and brain in modern medicine.Based on the understanding of"heart and brain co-dominating the mind",this paper be-lieves that"restlessness of mind"is the core pathogenesis of insomnia,and regulating mind is the key to the acupuncture and moxibus-tion treatment of insomnia.The autonomic nervous system(ANS)is a bridge connecting the heart and brain,and is closely related to the central anatomy,neurotransmitters and physiological rhythms of sleep.The imbalance of ANS is highly consistent with the patho-genesis of"heart and brain restlessness"in traditional Chinese medicine.The Governor Vessel runs through the brain and the heart,and the"Governor Vessel regulating spirit acupuncture"can communicate the heart and brain,regulate ANS function,and thus im-prove sleep quality.
6.The impact of the "daily-monthly-quarterly" quality control model on nursing quality based on total quality management theory
Jiaming DU ; Yinghui ZHANG ; Cailing WANG ; Yuping TANG ; Liyu ZHANG
Chinese Journal of Practical Nursing 2025;41(21):1630-1636
Objective:To explore the implementation method of the "daily-monthly-quarterly" quality control model based on total quality management (TQM) theory in nursing quality management, and evaluate its application effectiveness.Methods:A quasi-experimental research method was used. The quarterly quality control model employed at Shanxi Medical University Second Hospital from 2018 to 2019 was set as the control group, and the"day-month-quarter" quality control model based on TQM implemented from 2020 to 2022 was set as the observation group. The nurse practice environment assessment scores from 2018 to 2022 were analyzed; the nursing quality-sensitive indicators between the two groups were compared, including the incidence rate of overall adverse event, falls among hospitalized patients, pressure ulcers of stage 2 and above, unplanned extubations, and catheter-related infections (central venous catheter-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections).Results:The nurse practice environment assessment scores from 2018 to 2022 were (69.11 ± 19.66), (75.20 ± 18.70), (77.60 ± 17.65), (82.45 ± 16.44), and (88.00 ± 15.06). The differences compared to the previous year were statistically significant ( t=3.63-9.24, all P<0.05).After the intervention, the incidence rates of overall adverse events, falls among hospitalized patients, unplanned extubation, central venous catheter-related bloodstream infections, and ventilator-associated pneumonia in the control group were 0.385% (499/129 678), 0.072% (94/129 678), 0.051% (66/129 678), 0.037% (23/62 390), and 0.746% (43/5 761). Compared to 0.258% (551/213 851), 0.048% (103/213 851), 0.033% (71/213 851), 0.019% (19/98 642), and 0.444% (88/19 826) in the observation group. The differences were statistically significant ( χ2values were 3.89-42.83, all P<0.05). There were no statistically significant differences in the incidence rates of pressure ulcers of stage 2 and above and catheter-associated urinary tract infections (both P>0.05). Conclusions:The "daily-monthly-quarterly" quality control model based on TQM is beneficial in improving nursing quality and ensuring patient safety.
7.The Scientific Connotation of"Heart and Brain Co-Dominating the Mind"and Its Application in the Treatment of Insomnia by Acupuncture
Yuting ZHANG ; Shan QIN ; Xiaoqiu WANG ; Liyu LIN ; Mufeng LI ; Wenzhong WU ; Chengyong LIU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):181-188
The paper discusses the scientific connotation of"heart and brain co-dominating the mind",including the connotation of"heart and brain co-dominating the mind"in traditional Chinese medicine and the physiological and pathological relationship be-tween heart and brain in modern medicine.Based on the understanding of"heart and brain co-dominating the mind",this paper be-lieves that"restlessness of mind"is the core pathogenesis of insomnia,and regulating mind is the key to the acupuncture and moxibus-tion treatment of insomnia.The autonomic nervous system(ANS)is a bridge connecting the heart and brain,and is closely related to the central anatomy,neurotransmitters and physiological rhythms of sleep.The imbalance of ANS is highly consistent with the patho-genesis of"heart and brain restlessness"in traditional Chinese medicine.The Governor Vessel runs through the brain and the heart,and the"Governor Vessel regulating spirit acupuncture"can communicate the heart and brain,regulate ANS function,and thus im-prove sleep quality.
8.The impact of the "daily-monthly-quarterly" quality control model on nursing quality based on total quality management theory
Jiaming DU ; Yinghui ZHANG ; Cailing WANG ; Yuping TANG ; Liyu ZHANG
Chinese Journal of Practical Nursing 2025;41(21):1630-1636
Objective:To explore the implementation method of the "daily-monthly-quarterly" quality control model based on total quality management (TQM) theory in nursing quality management, and evaluate its application effectiveness.Methods:A quasi-experimental research method was used. The quarterly quality control model employed at Shanxi Medical University Second Hospital from 2018 to 2019 was set as the control group, and the"day-month-quarter" quality control model based on TQM implemented from 2020 to 2022 was set as the observation group. The nurse practice environment assessment scores from 2018 to 2022 were analyzed; the nursing quality-sensitive indicators between the two groups were compared, including the incidence rate of overall adverse event, falls among hospitalized patients, pressure ulcers of stage 2 and above, unplanned extubations, and catheter-related infections (central venous catheter-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections).Results:The nurse practice environment assessment scores from 2018 to 2022 were (69.11 ± 19.66), (75.20 ± 18.70), (77.60 ± 17.65), (82.45 ± 16.44), and (88.00 ± 15.06). The differences compared to the previous year were statistically significant ( t=3.63-9.24, all P<0.05).After the intervention, the incidence rates of overall adverse events, falls among hospitalized patients, unplanned extubation, central venous catheter-related bloodstream infections, and ventilator-associated pneumonia in the control group were 0.385% (499/129 678), 0.072% (94/129 678), 0.051% (66/129 678), 0.037% (23/62 390), and 0.746% (43/5 761). Compared to 0.258% (551/213 851), 0.048% (103/213 851), 0.033% (71/213 851), 0.019% (19/98 642), and 0.444% (88/19 826) in the observation group. The differences were statistically significant ( χ2values were 3.89-42.83, all P<0.05). There were no statistically significant differences in the incidence rates of pressure ulcers of stage 2 and above and catheter-associated urinary tract infections (both P>0.05). Conclusions:The "daily-monthly-quarterly" quality control model based on TQM is beneficial in improving nursing quality and ensuring patient safety.
9.The changes in retinal and choroidal blood after scleral buckling surgery for rhegmatogenous retinal detachment
Liyu REN ; Xiaoli LI ; Shiyong XIE ; Quanhong HAN ; Ying WANG
Chinese Journal of Ocular Fundus Diseases 2025;41(5):349-357
Objective:To observe the hemodynamic changes in the retina and choroid after scleral buckling surgery in eyes with rhegmatogenous retinal detachment (RRD).Methods:A prospective clinical observational study. A total of 25 eyes of 25 patients with RRD who underwent scleral buckling surgery in Tianjin Eye Hospital from February to April 2024 were included in the study. Among them, 10 were male and 15 were female. Age was 17-68 years old. All cases were monocular. The surgical eye and the contralateral healthy eye were divided into the affected eye group and the contralateral healthy eye group respectively. Best corrected visual acuity (BCVA), scanning source optical coherence tomography angiography (SS-OCTA), and axial length (AL) measurements were performed 3 months after surgery. SS-OCTA examination of macular area was performed by VG200 of Visual Microimaging (Henan) Technology Co., LTD. Scanning range 21 mm×26 mm. According to the partitioning method of the early treatment group of glycosuria retinopathy, the retina within 21 mm of the macular fovea was divided into concentric circles with the macular fovea as the center and diameters of 1-3, 3-6, 6-12, 12-21 mm, respectively. The built-in software of the device was used to record the central area (12 mm×12 mm in the fovea of the macula) and the peripheral area (12-21 mm range) retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), radial peripapillary capillaries (RPC) blood density and choroidal vascular index (CVI), choroidal vascular volume (CVV), and 1-3, 3-6, 6-12, 12-21 mm above concentric circles (S), nasal side (N), temporal side (T), and lower side (I) SCP, DCP, and RPC blood flow density. Quantitative data between the two groups were compared by independent sample t test or Wilcoxon signed rank test. The correlation between retinal and choroid blood flow parameters and postoperative BCVA was analyzed by Spearman correlation analysis. Results:Compared with the opposite healthy eye group, SCP blood density in the central area ( Z=-4.372), DCP blood density in the central area ( Z=-2.829), and CVI in the peripheral area ( Z=-2.138) were decreased in the affected eye group, and the differences were statistically significant ( P<0.05). SCP: in the affected eye group, the blood flow density in T 3-6 mm, T 6-12 mm, N 6-12 mm and T 12-21 mm regions decreased, while the blood flow density in I 6-12 mm regions increased, with statistical significance ( P<0.05). DCP: blood flow density in S 6-12 mm, I 6-12 mm, S 12-21 mm and I 12-21 mm regions decreased significantly, and the differences were statistically significant ( P<0.05). RPC: blood flow density decreased significantly in T 6-12 mm and I 12-21 mm, and the differences were statistically significant ( P<0.05). CVI: T 6-12 mm, S 12-21 mm, T 12-21 mm, I 12-21 mm significantly decreased, and T 1-3 mm, S 12-21 mm significantly increased, the differences were statistically significant ( P<0.05). Correlation analysis showed that AL growth was positively correlated with CVV in central region ( r=0.408, P=0.040). The number of pad pressure was negatively correlated with the blood density of central DCP ( r=-0.422, P=0.030). Conclusions:After scleral buckling operation, the blood flow density and choroidal blood flow parameters in RRD affected eyes are lower than those in contralateral healthy eyes in some areas. The increase of AL is positively correlated with CVV in the central region, and the wider the range of pad pressure, the worse the recovery of DCP blood density.
10.Clinical phenotype, genetic characteristics, and creation of immortalized cell lines for patients from a pedigree affected with Hunter syndrome
Benchang LI ; Fengyu CHE ; Lidangzhi MO ; Liyu ZHANG ; Guoxia WANG ; Ying YANG
Chinese Journal of Medical Genetics 2024;41(8):916-924
Objective:To explore the clinical phenotype and genetic variant in a Chinese pedigree affected with Hunter syndrome and create immortalized cell lines for the affected pedigree members.Methods:A pedigree of six members who had visited Xi′an Children′s Hospital in July 2022 was selected as the study subject. Clinical data was collected. Whole exome sequencing was carried out for the pedigree members. Candidate variant was verified by Sanger sequencing. In addition, peripheral B lymphocytes were transfected with Epstein-Barr virus to create immortalized cell lines, which were then subjected to enzyme activity analysis.Results:The patient, a five-year-and-seven-month-old boy, had exhibited stiff limbs and enlarged joints. He had developed hernia, scaphocephaly, and barrel chest from 3 months of age. His uncle also had stiff limbs, poor hearing, blindness, and right oblique inguinal hernia. Above features had resembled those of Hunter syndrome. Genetic testing revealed that both the child and his uncle had harbored an IDS (NM_000202.8): c. 823G>A (p.D275N) variant, which was unreported previously. Bioinformatic analysis indicated that the D275 to be a highly conserved site, and the D275N variant may affect the stability of the protein′s spatial conformation, thereby decrease the catalytic activity of the enzyme. The successfully constructed immortalized lymphoblastoid cell lines for the child and his parents showed increased volume, irregular shape, burr structure and cluster growth. And the value of IDS activity of the patient′s immortalized lymphoblastoid cells was below the limit of detection. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS3+ PM2_Supporting+ PM5+ PP1+ PP3). Conclusion:Above finding has enriched the phenotypic and mutational spectra of Hunter syndrome, and provided a basis for the genetic counseling for this pedigree. The creation of immortalized cell lines has offered a model for further investigation of the impact of variant on the function of IDS and development of targeted drugs.


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