1.The Role of Mechanical Sensitive Ion Channel Piezo in Digestive System Diseases
Si-Qi WANG ; Xiang-Yun YAN ; Yan-Qiu LI ; Fang-Li LUO ; Jun-Peng YAO ; Pei-Tao MA ; Yu-Jun HOU ; Hai-Yan QIN ; Yun-Zhou SHI ; Ying LI
Progress in Biochemistry and Biophysics 2024;51(8):1883-1894
The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.
2.Raman Spectroscopy Analysis of The Temporal Heterogeneity in Lung Cell Carcinogenesis Induced by Benzo(a)pyrene
Hai-Tao ZHOU ; Wei YAO ; Cao-Zhe CUI ; Xiao-Tong ZHOU ; Xi-Long LIANG ; Cheng-Bing QIN ; Lian-Tuan XIAO ; Zhi-Fang WU ; Si-Jin LI
Progress in Biochemistry and Biophysics 2024;51(6):1458-1470
ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.
3.Study on the nutritional value of human protein synthesized from six balanced compound amino acid injections
Hai-Ling DI ; Ling-Zhi FANG ; Yao LI ; Ze-Fang YU ; Yu-Pei WU ; Ying-Qin SHI
Parenteral & Enteral Nutrition 2024;31(3):143-146,153
Objective:To provide reference for hospital drug selection and clinical rational drug selection,through evaluating the nutritional value of six commonly used balanced compound amino acid injection (BCAA) in clinical practice,including 18AA (250 mL:12.5 g),18AA-I (250 mL:17.5 g),18AA-Ⅱ(250 mL:21.25 g),18AA-IV (250 mL:8.7 g),18AA-V (250 mL:8.06 g),and 18AA-V-SF (250 mL:8.06 g). Methods:Based on the whole egg protein model,the nutritional value of six varieties of BCAA from two aspects were evaluated,including the first limiting amino acid chemical score (CS),value of essential amino acid (EAA) and the comprehensive quality of total EAA (both essential amino acid index and closeness to standard protein). Results:The first limiting amino acid CS value from high to low was 18AA-Ⅱ>18AA>18AA-V=18AA-V-SF>18AA-I=18AA-Ⅳ. Total EAA comprehensive quality:the essential amino acid index from high to low was 18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. The closeness to whole egg protein from high to low was 18AA-Ⅱ=18AA=18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Ultimately,the nutritional value of the 6 varieties of BCAA decreased from high to low:18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Conclusions:Among the six varieties of BCAA,18AA-Ⅱ has the highest nutritional value and the highest amino acid content in the same liquid volume,making it the preferred drug for patients with normal liver and kidney function.
4.Determination of effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation for pediatric MRI:a modified sequential study
Jian TANG ; Jin-Peng QIU ; Hai-Ya TU ; Jia-Lian ZHAO ; Yao-Qin HU
Medical Journal of Chinese People's Liberation Army 2024;49(8):876-880
Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image(MRI).Methods This is a prospective modified sequential study.Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023,aged 1 month to 6 years old,with a weight of 6.0-23.5 kg,were enrolled in this study.All children received 0.5 mg/kg oral midazolam,followed by intranasal dexmedetomidine.The initial dose of dexmedetomidine was 0.5 μg/kg,and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg.Probit analysis was used for calculating the half effective dose(ED50),95%effective dose(ED95)and the corresponding 95%confidence interval(CI)of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI.The sedation onset time,wake-up time,vital signs and adverse reactions were recorded.Results Among all the children,the sedation onset time of successful sedation children was(31.21±7.47)min,and the wake-up time was(81.21±26.04)min.The ED50 for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg,with a 95%CI of 0.302-0.461 μg/kg;the ED95 was 0.549 μg/kg,with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference(P<0.05)in heart rate and diastolic blood pressure after sedation compared to the baseline before medication.Two cases of restlessness during the awakening period were observed,but no other adverse reactions occurred.Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive,easy to implement,safe,and effective.It can be widely used in pediatric MRI.
5.Phylogenetic analysis of chloroplast genome of Tussilago farfara L.
Yi-yao JING ; Ben-xiang HU ; Xiao-ying CHEN ; Hai-yue JI ; Yao LUO ; Jia-zhou SHI ; Bang-qing WANG ; Gang ZHANG ; Jing GAO ; Bing-yue YANG ; Liang PENG
Acta Pharmaceutica Sinica 2023;58(11):3439-3448
italic>Tussilago farfara L. is a perennial herb of
6.Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation.
Ze WEI ; Shun Qiao FENG ; Xiao Yu YI ; Qin LUO ; Hai Jun DU ; Guo Yong MEI ; Rong LIU ; Hai Lan YAO ; Jun HAN
Chinese Journal of Preventive Medicine 2023;57(12):2095-2101
Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
Male
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Humans
;
Child
;
Female
;
Immune Reconstitution
;
Retrospective Studies
;
Cytomegalovirus Infections
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
CD8-Positive T-Lymphocytes
7.Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling.
Lu WANG ; Ying CHEN ; Ming-Min XU ; Wei CAO ; Qian-Hua ZHENG ; Si-Yuan ZHOU ; Jun-Peng YAO ; Meng-Han XI ; Hai-Yan QIN ; Ying LI ; Wei ZHANG
Chinese journal of integrative medicine 2023;29(5):459-469
OBJECTIVE:
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
METHODS:
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
RESULTS:
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.
CONCLUSION
EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.
Mice
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Animals
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Proto-Oncogene Proteins c-akt/metabolism*
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Phosphatidylinositol 3-Kinases/metabolism*
;
Electroacupuncture
;
Beclin-1
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Signal Transduction
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Constipation/therapy*
;
TOR Serine-Threonine Kinases/metabolism*
;
Autophagy
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Neuroglia/metabolism*
;
Mammals/metabolism*
8.DCK confers sensitivity of DCTD-positive cancer cells to oxidized methylcytidines.
Ya-Hui ZHAO ; Wei JIANG ; Hai GAO ; Guo-Zheng PANG ; Yu-Shuang WU ; Yuan-Xian WANG ; Meng-Yao SHENG ; Jia-Ying XIE ; Wan-Ling WU ; Zhi-Jian JI ; Ya-Rui DU ; Lei ZHANG ; Xiao-Qin WANG ; Colum P WALSH ; Hai JIANG ; Guo-Liang XU ; Dan ZHOU
Protein & Cell 2023;14(7):532-537
9.Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation.
Ze WEI ; Shun Qiao FENG ; Xiao Yu YI ; Qin LUO ; Hai Jun DU ; Guo Yong MEI ; Rong LIU ; Hai Lan YAO ; Jun HAN
Chinese Journal of Preventive Medicine 2023;57(12):2095-2101
Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
Male
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Humans
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Child
;
Female
;
Immune Reconstitution
;
Retrospective Studies
;
Cytomegalovirus Infections
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
CD8-Positive T-Lymphocytes
10.Relationship between body mass index and sexual development in Chinese children.
Xiao Qin XU ; Jian Wei ZHANG ; Rui Min CHEN ; Jing Si LUO ; Shao Ke CHEN ; Rong Xiu ZHENG ; Di WU ; Min ZHU ; Chun Lin WANG ; Yan LIANG ; Hui YAO ; Hai Yan WEI ; Zhe SU ; Mireguli MAIMAITI ; Hong Wei DU ; Fei Hong LUO ; Pin LI ; Shu Ting SI ; Wei WU ; Ke HUANG ; Guan Ping DONG ; Yun Xian YU ; Jun Fen FU
Chinese Journal of Pediatrics 2022;60(4):311-316
Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent
;
Body Mass Index
;
Child
;
Child, Preschool
;
China/epidemiology*
;
Cross-Sectional Studies
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Female
;
Humans
;
Male
;
Obesity/epidemiology*
;
Overweight/epidemiology*
;
Puberty
;
Puberty, Precocious
;
Sexual Development

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