Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare autosomal dominant genetic disorder. It may also involve many other organ systems, leading to complications such as exocrine pancreatic insufficiency, liver dysfunction, lymphedema, and developmental delay. The FAM111B has been determined as the pathogenic gene associated with POIKTMP syndrome, whose protein product plays a critical role in regulating essential cellular processes including DNA repair and replication, cell cycle progression, apoptosis, nuclear transport, and telomere length maintenance. This article has provided a comprehensive review for the genetic basis of POIKTMP syndrome and its correlation with various phenotypes, which may offer insights for basic research and clinical diagnosis of this disease.
Humans ; Pulmonary Fibrosis/genetics* ; Skin Diseases, Genetic/genetics*

Objective To explore the roles of the mechanoreceptor Yes-associated protein 1(YAP1)and piezo type mechanosensitive ion channel component 2(PIEZO2)in mechanotransduction in mouse bladder urothelial cells.Methods Mouse bladder urothelial cells were subjected to mechanical stretching using the FX-6000T cell stretching system and treated with the YAP1-specific inhibitor verteporfin(VP).The expressions of PIEZO2,YAP1 and connective tissue growth factor(CTGF)at the mRNA and protein levels,as well as changes in cellular adenosine triphosphatase(ATP)concentration,were detected using reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB).Results After stretching stimulation,under the fluorescence microscope,it was observed that the diameter length of the stretched cells were longer than that before stretching,and the difference was statistically significant(P＜0.05).The expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels were increased in the stretched group compared to those of the non-stretched group(P＜0.05).VP effectively reduced the expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels after stretching stimulation(P＜0.05).Stretching stimulation significantly increased the intracellular ATP concentration,while VP was able to inhibit the increase in ATP concentration,with a statistically significant difference(P＜0.000 1).Conclusion Stretching stimulation increased the expressions of YAP1 and PIEZO2 in bladder urothelial cells and promoted the release of ATP;verteporfin inhibited the increase in YAP1 activity and the overexpression of PIEZO2 caused by stretching,thereby reducing the release of ATP.It is suggested that mouse bladder urothelial cells may primarily sense mechanical signals through the YAP1-PIEZO2-ATP pathway.

Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the CLCN5 gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination. Comprehensive biochemical testing and clinical evaluation revealed significant LMWP and hypercalciuria, while renal biopsy showed mesangial cell and matrix proliferation. Whole exome sequencing identified a novel deletion mutation in the CLCN5 gene (NM_001127899.4, c.1158delC, p.F387Lfs*42) causing a frameshift and premature termination, which is likely to disrupt its role in chloride/hydrogen ion exchange and endosomal acidification. Bioinformatic analysis indicated the variant is pathogenic. Genetic testing plays an important role in diagnosing rare kidney diseases. Early identification of pathogenic mutations is essential for facilitating timely intervention and appropriate management, potentially enhancing patient outcomes. This report expands the CLCN5 mutation spectrum and contributes to understanding the genetic and molecular mechanisms of Dent disease.
Humans ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Male ; Child ; Computational Biology ; Mutation ; Proteinuria/genetics* ; Hypercalciuria/genetics*

Objective:With the aging of the population, the health of women's ovarian in China has received increasing attention.Ovarian aging not only affects reproductive health but also increases the risk of chronic diseases.This study aims to systematically explore the relationship between living habits and ovarian aging.Methods:Based on the data from the China Health and Retirement Longitudinal Study(CHARLS)from 2011 to 2018, 8 287 postmenopausal women were included.A retrospective cohort study was conducted using statistical analysis and machine learning methods to evaluate the impact of lifestyle factors such as smoking, drinking, sleep, and dietary patterns on the age of menopause.Results:It was found that adverse lifestyle factors such as reduced daily meal frequency [the early menopause group(2.85±0.38)times/day vs.the normal group(2.89±0.38)times/day, P=0.002], smoking [the smoking rate of the early menopause group(7.75%) vs.that of the normal group(6.15%), P=0.004], and high-frequency drinking [the early menopause rate of people who drink daily(19.76%(33/167)) vs.that of people who rarely or never drink(14.62%(1 162/7 949)), P=0.047]were associated with accelerated ovarian aging. Conclusions:Reasonable adjustment of living habits maybe help to delay the age of menopause and reduce related health risks.This study provides a scientific basis for optimizing women's healthy lifestyles, which is conducive to improving the quality of life and happiness of middle-aged and elderly women in China.

Objective:With the aging of the population, the health of women's ovarian in China has received increasing attention.Ovarian aging not only affects reproductive health but also increases the risk of chronic diseases.This study aims to systematically explore the relationship between living habits and ovarian aging.Methods:Based on the data from the China Health and Retirement Longitudinal Study(CHARLS)from 2011 to 2018, 8 287 postmenopausal women were included.A retrospective cohort study was conducted using statistical analysis and machine learning methods to evaluate the impact of lifestyle factors such as smoking, drinking, sleep, and dietary patterns on the age of menopause.Results:It was found that adverse lifestyle factors such as reduced daily meal frequency [the early menopause group(2.85±0.38)times/day vs.the normal group(2.89±0.38)times/day, P=0.002], smoking [the smoking rate of the early menopause group(7.75%) vs.that of the normal group(6.15%), P=0.004], and high-frequency drinking [the early menopause rate of people who drink daily(19.76%(33/167)) vs.that of people who rarely or never drink(14.62%(1 162/7 949)), P=0.047]were associated with accelerated ovarian aging. Conclusions:Reasonable adjustment of living habits maybe help to delay the age of menopause and reduce related health risks.This study provides a scientific basis for optimizing women's healthy lifestyles, which is conducive to improving the quality of life and happiness of middle-aged and elderly women in China.

Objective To explore the roles of the mechanoreceptor Yes-associated protein 1(YAP1)and piezo type mechanosensitive ion channel component 2(PIEZO2)in mechanotransduction in mouse bladder urothelial cells.Methods Mouse bladder urothelial cells were subjected to mechanical stretching using the FX-6000T cell stretching system and treated with the YAP1-specific inhibitor verteporfin(VP).The expressions of PIEZO2,YAP1 and connective tissue growth factor(CTGF)at the mRNA and protein levels,as well as changes in cellular adenosine triphosphatase(ATP)concentration,were detected using reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB).Results After stretching stimulation,under the fluorescence microscope,it was observed that the diameter length of the stretched cells were longer than that before stretching,and the difference was statistically significant(P＜0.05).The expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels were increased in the stretched group compared to those of the non-stretched group(P＜0.05).VP effectively reduced the expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels after stretching stimulation(P＜0.05).Stretching stimulation significantly increased the intracellular ATP concentration,while VP was able to inhibit the increase in ATP concentration,with a statistically significant difference(P＜0.000 1).Conclusion Stretching stimulation increased the expressions of YAP1 and PIEZO2 in bladder urothelial cells and promoted the release of ATP;verteporfin inhibited the increase in YAP1 activity and the overexpression of PIEZO2 caused by stretching,thereby reducing the release of ATP.It is suggested that mouse bladder urothelial cells may primarily sense mechanical signals through the YAP1-PIEZO2-ATP pathway.

Objective:To explore the acupoint selection law in acupuncture and moxibustion in treating postpartum incontinence by using data mining technology.Methods:The clinical research literature on acupuncture and moxibustion treatment for postpartum incontinence was retrieved from CNKI, Wanfang Data, VIP, CBM, China Medical Journal Full-text Database, PubMed, Embase, Web of Science from the establishment of the databases to February 1, 2023. The acupoint prescription database was established using Excel 2016 and conducting frequency statistics of acupoints, meridians and specific acupoints. Clustering analysis was performed using SPSS Statistics 25.0, and association rule analysis was performed using SPSS Modeler 18.0.Results:A total of 70 articles were included, involving 70 acupuncture prescriptions and including 31 acupoints with a total frequency of 384 times. The top five acupoints were Sanyinjiao (SP6, 46 times), Guanyuan (CV4, 45 times), Zusanli (ST36, 43 times), Zhongji (RN3, 41 times), and Qihai (CV6, 38 times). The commonly used meridians were Conception Vessel, bladder meridian and spleen meridian. The involved acupoints were mostly located in the lower limbs and belly, and most of them were Jiaohui, Mu and Wushu acupoints. Five effective clustering groups were obtained by clustering analysis of high frequency acupoints. The core acupoint combination of association rules was Sanyinjiao (SP6)-Zusanli (ST36)-Guanyuan (CV4)-Qihai (CV6)-Zhongji (RN3).Conclusions:The pathogenesis of postpartum urinary incontinence is mainly characterized by qi deficiency. Acupuncture and moxibustion treatment of postpartum urinary incontinence follows the principles of invigorating qi and tonifying spleen, nourishing lung and tonifying kidney, paying attention to the use of acupoints in abdomen and lower limbs, and using the methods of upper and lower acupoints, anterior and posterior acupoints.

Char syndrome is a rare autosomal dominant genetic disorder characterized by patent ductus arteriosus, facial dysmorphism, and dysplasia of fingers/toes. It may also be associated with multiple papillae, dental dysplasia, and sleep disorders. TFAP2B has proven to be a pathogenic gene for neural crest derivation and development, and several variants of this gene have been identified. Bone morphogenetic protein signaling plays an important role in embryonic development by participating in limb growth and patterning, and regulation of neural crest cell development. TFAP2B is an upstream regulatory gene for bone morphogenetic proteins 2 and 4. Variants of the TFAP2B gene may lead to abnormal proliferation of neural crest cells by affecting the expression of bone morphogenetic proteins, resulting in multiple organ dysplasia syndrome. In addition, TFAP2B variants may only lead to patent ductus arteriosus instead of typical Char syndrome.

Objective:To screen mutations of the adenosine triphosphate(ATP)-binding cassette transporter A3(ABCA3)gene in elderly Chinese individuals with lung interstitial diseases(ILDs)and to analyze the clinical characteristics of ILDs in elderly patients.Methods:A prospective study, After further image analysis of patients diagnosed with interstitial lung diseases between September 2015 and December 2018 at the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital of Central South University, 103 patients were willing to provide peripheral blood samples and signed informed consent.DNA samples were extracted and whole exome sequencing was performed to screen ABCA3 gene mutations.Clinical data of patients were summarized and analyzed.Results:Seven rare variants of the ABCA3 gene were identified in 6 patients, with a mean age of 67 years(69-73 years)and an equal sex distribution, and 33.3%(2/6)were smokers.The most notable presentation was diffuse lung lesions.Patients' final diagnoses included idiopathic pulmonary fibrosis(IPF, 3/6), nonspecific interstitial pneumonia(NSIP, 1/6), and IgG4-related lung disease(2/6). Meanwhile, compound heterozygous mutations of the ABCA3 gene responsible for IPF were identified in patient No.39, including p. Asp1465Asn, p.Leu3Vval and p. Val93Ile3, a new finding in patients with ILDs.Conclusions:ABCA3 mutation-related lung interstitial diseases exhibit variable characteristics, with differences in the age of onset, clinical manifestations, imaging features and prognosis between patients.ABCA3 mutations responsible for early-onset ILDs are mostly homozygous or compound heterozygous and usually highly pathogenic nonsense mutations.In contrast, ABCA3 mutations identified in elderly patients with ILDs are often missense mutations, a possible explanation for the variability of ILDs in the elderly.Since patients with ILDs caused by ABCA3 variants respond poorly to currently available treatment options, early genetic diagnosis may benefit patients by enhancing disease awareness.

Objective To investigate the correlations between lipoprotein associated phospholipase A2(Lp-PLA2),platelet aggregation rate(PAG),the ratio of mean platelet volume to platelet count(MPV/PLT)and major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease(CHD).Methods The clinical data of 162 elderly patients with CHD admitted to Jianhu Hospital affiliated to Nantong University from August 2020 to September 2021 were collected retrospectively.All the patients were treated with aspirin orally and followed up for 1 year.The development of MACE within 1 year was recorded.MACE occurred in 30 patients(development group)and the other 132 patients without MACE were assigned to non-development group.Serum Lp-PLA2,PAG,and MPV/PLT were compared between the 2 groups at admission.Logistic regression was used to analyze the relationship between these parameters and MACE in elderly CHD patients.Receiver operating character(ROC)curve was used to evaluate the value of serum Lp-PLA2,PAG,MPV/PLT alone and jointly at admission in predicting MACE within 1 year.Results The proportions of patients with age≥75 years and hypertension in the development group were significantly higher than those in the non-development group(P<0.05).Serum Lp-PLA2,PAG,MPV/PLT in the development group were also significantly higher than those in the non-development group(P<0.05).Binary logistic regression analysis showed that hypertension,Lp-PLA2,PAG,and MPV/PLT were influence factors of MACE in elderly CHD patients(P<0.05).ROC curve results showed that the area under curve(AUC)values of Lp-PLA2,PAG,MPV/PLT alone or jointly were 0.832,0.817,0.841 and 0.939 in predicting MACE in elderly CHD patients.Conclusion Overexpression of Lp-PLA2,PAG and MPV/PLT are closely related to the development of MACE in elderly CHD patients.During hospitalization,the risk of MACE can be assessed by detecting Lp-PLA2,PAG,and MPV/PLT,and timely clinical intervention can be carried out.