Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Objective:To explore the relationship between the prognostic nutritional index(PNI)and the prevalence of coronary heart disease(CHD)in adults.Methods:A cross-sectional analysis was conducted based on the 2017-2020 National Health and Nutrition Examination Survey(NHANES)database.A total of 12,141 adult participants were initially included and divided into CHD group and control group according to the disease status questionnaire.PNI was calculated using serum albumin level and lymphocyte count.Multivariable logistic regression was applied to explore the association between PNI and the prevalence of CHD in adults.Subgroup analysis was conducted to assess whether this association remained consistent across different populations.A restricted cubic spline model was con-structed to clarify the dose-response relationship between PNI and CHD prevalence in adults.Results:Among the 3,894 adult participants,200(5.14％)had CHD.The PNI level in CHD patients was significantly lower than that of the control group[(49.20±8.59)vs.(51.57±4.80),P＜0.001].Multivariable logistic regression analysis showed that,after adjustment for sex,age,race,marital status,body mass index(BMI),hypertension,diabetes and family history of cardiovascular disease,an increase in PNI was still independently associated with a lower prev-alence of CHD(odds ratio[OR]=0.92,95％CI 0.89～0.94,P＜0.001).The dose-response relationship indica-ted a negative linear correlation between PNI and CHD prevalence(P＜0.001).Subgroup analysis showed that the association between PNI and CHD differed significantly across BMI,hypertension and diabetes subgroups(P for in-teraction＜0.05 or＜0.01).Conclusion:Increasing PNI was significantly associated with a lower prevalence of CHD in adults,and this association was more pronounced in specific high-risk populations,such as those with obe-sity,hypertension,and diabetes.Our findings suggest that maintaining good nutritional status is of great significance in reducing the risk of CHD.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective:To explore the relationship between the prognostic nutritional index(PNI)and the prevalence of coronary heart disease(CHD)in adults.Methods:A cross-sectional analysis was conducted based on the 2017-2020 National Health and Nutrition Examination Survey(NHANES)database.A total of 12,141 adult participants were initially included and divided into CHD group and control group according to the disease status questionnaire.PNI was calculated using serum albumin level and lymphocyte count.Multivariable logistic regression was applied to explore the association between PNI and the prevalence of CHD in adults.Subgroup analysis was conducted to assess whether this association remained consistent across different populations.A restricted cubic spline model was con-structed to clarify the dose-response relationship between PNI and CHD prevalence in adults.Results:Among the 3,894 adult participants,200(5.14％)had CHD.The PNI level in CHD patients was significantly lower than that of the control group[(49.20±8.59)vs.(51.57±4.80),P＜0.001].Multivariable logistic regression analysis showed that,after adjustment for sex,age,race,marital status,body mass index(BMI),hypertension,diabetes and family history of cardiovascular disease,an increase in PNI was still independently associated with a lower prev-alence of CHD(odds ratio[OR]=0.92,95％CI 0.89～0.94,P＜0.001).The dose-response relationship indica-ted a negative linear correlation between PNI and CHD prevalence(P＜0.001).Subgroup analysis showed that the association between PNI and CHD differed significantly across BMI,hypertension and diabetes subgroups(P for in-teraction＜0.05 or＜0.01).Conclusion:Increasing PNI was significantly associated with a lower prevalence of CHD in adults,and this association was more pronounced in specific high-risk populations,such as those with obe-sity,hypertension,and diabetes.Our findings suggest that maintaining good nutritional status is of great significance in reducing the risk of CHD.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the correlation between systemic family dynamics characteristics and adolescent depressive symptoms,and the mediating role of negative life events between them.Methods A cross-sectional study was conducted on 124 adolescent patients diagnosed with depressive disorder according to the international classification of diseases(ICD)-10 criteria at the Psychosomatic Medicine Department of Shanghai East Hospital Affiliated to Tongji University from September 2021 to February 2023.The second edition of the Scale of Systematic Family Dynamics(SSFD),Children's Depression Inventory(CDI),and Adolescent Self-Rating Life Events Checklist(ASLEC)were utilized to evaluate the family dynamics characteristics,depressive symptoms,and negative life events.Canonical correlation analysis was performed to explore the relationships between 4 dimensions of SSFD[family atmosphere(FA),individuation(IN),system logic(SL),illness concept(IC)]and 5 factors of CDI(low self-esteem,negative emotion,anhedonia,inefficiency,interpersonal problem).A mediation effect analysis using Bootstrap test was conducted to analyze the mediating role of negative life events between family dynamics and adolescent depressive symptoms.Results The scores for FA,SL,and IN in SSFD were negatively correlated with the total score of CDI(r=-0.359,-0.256,-0.291,P<0.01),and negatively correlated with the total score of ASLEC too(r=-0.318,-0.371,-0.406,P<0.01).However,a positive correlation was observed between the total scores of ASLEC and CDI(r=0.633,P<0.01).Canonical correlation analysis between the 4 dimensions of SSFD and the 5 factors of CDI revealed one pair of statistically significant canonical variables(U1,V1)with a canonical correlation coefficient of 0.483(P<0.05).This indicates that the canonical variable U1 of SSFD was primarily influenced by FA,while the canonical variable V1 of CDI was mainly affected by low self-esteem and interpersonal problems.The mediating analysis showed that the effects of FA,IN,and SL scores on CDI total score were all weak(-0.147,-0.117,-0.102,respectively)but statistically significant(P<0.05).The direct effect of IN and SL scores on CDI total score was not statistically significant(P>0.05),while the direct effect of FA score on CDI total score was statistically significant(-0.076,P<0.05).Additionally,the mediating effect of ASLEC between the scores of FA,IN,SL and CDI total score were all significant(-0.071,-0.095,-0.087,respectively)(P<0.05).Conclusions Adolescent depressive symptoms may be influenced by systemic family dynamics characteristics and negative life events.Negative life events mediate the influence of FA,IN,and SL on depressive symptoms.However,the IC is not related to depressive symptoms in adolescents.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies