Objective To investigate the role of member septin family(SEPT12)in human spermatogenesis and its influence on sperm motility and sperm ultrastructure.Methods Whole exome sequencing(WES)was performed on peripheral blood DNA extracted from 375 patients with asthenoteratozoospermia,and a patient with idiopathic in-fertility carrying compound heterozygous mutation of SEPT12 was screened out.Sanger sequencing was performed to verify the mutation,and co-segregation analysis was performed in the family.The morphological abnormalities of sperm were analyzed by hematoxylin-eosin(HE)staining and scanning electron microscopy(SEM),and the ultra-structural defects of sperm were analyzed by transmission electron microscopy(TEM).Then the effects of the muta-tion on the level and position of the protein and the changes of the location and level of the defect structure markers were analyzed by Western blot and immune-fluorescence(IF).Results The compound heterozygous mutations c.C332A(p.Ti111K)and c.406_416 del TGCTCGTATTG(p.q136 VFS*39)in the SEPT12 gene were screened and identified in a patient with asthenoteratozoospermia.The mutations were verified by Sanger sequencing,which was consistent with the co-segregation genetic pattern of the family.The mutations resulted in loss of protein expres-sion,decreased sperm motility and sperm morphological deformities,mainly including short tail,curly tail and ir-regular sperm head.The ultrastructure of sperm showed that the annulus between the mid-piece and the principle-piece was missing,the acrosome membrane of sperm head fell off and the nucleus contained vacuoles.In the mid-piece of sperm flagella,the arrangement of mitochondrial sheath was disordered,most of flagella axoneme central pair was absent,microtubules doublet was missing or disordered,and some radical spoke was absent.By Western blot and IF,the marker proteins of related structural components were detected,and the results showed that the level of SEPT4 protein decreased,SEPT6 protein unchanged,acrosomal related proteins ACTL7A and ACROSIN protein missing,and the expression levels of mitochondrial and axoneme related proteins TOMM20,SPAG6 and RSPH3 protein significantly decreased.Conclusion The deletion of SEPT12 protein caused by SEPT12 gene mu-tation leads to the deletion of the annulus between the mid-piece and the principle-piece,and the abnormal assem-bly of sperm acrosome,mitochondrial sheath and flagella.

Background::With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods::We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).Results::There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion::For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [⁶⁴Cu]DPA and investigated the tumor engagement of [⁶⁴Cu/⁶⁸Ga]DPA in mouse models. Our results revealed that intact [⁶⁴Cu/⁶⁸Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [⁶⁴Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

Objective:To analyze the clinical phenotype, imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene (TREM2).Methods:Clinical data were collected from a patient with early-onset dementia. Then whole exome sequencing was performed for the proband, followed by Sanger sequencing for the family members.Results:The clinical manifestations of the proband (a 49-year-old female) was personality changes, mental and behavioral abnormalities, memory loss, ataxia, and seizures. Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2, namely c.154C>T (p.R52C) heterozygosity in four family members, and one patient with similar clinical manifestations was deceased. The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy, bilateral white matter hyperintensity, thin corpus callosum. No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions:A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia, epilepsy, but without bone cysts. This mutation is probably pathogenic. This research highlights the importance of TREM2 gene mutation screening in early-onset dementia, especially in those with atypical presentations.

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with F-flurodeoxyglucose (F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

PURPOSE: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. MATERIALS AND METHODS: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. RESULTS: After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. CONCLUSION: Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.
Breast ; Cohort Studies ; Colorectal Neoplasms ; Electronic Health Records ; Humans ; Insulin ; Lung ; Metformin ; Mortality ; Proportional Hazards Models ; Stomach Neoplasms

Objective: To study the correlation between job satisfaction and work effectiveness of ICU specialist nurses, to clarify the baseline level and influence factors, to increase the efficiency and satisfaction of the work, and to stabilize the ICU nurse team, to improve the quality of care. Methods: The convenience sampling method was used to select 116 specialist nurses from the 3 three grade ICU hospitals in Guangzhou. Through the questionnaire survey of nurses′ general situation, work efficiency and job satisfaction, the methods of descriptive statistics, average number, standard deviation analysis, simple linear regression model analysis and multiple linear regression analysis were adopted to reveal the relationship between work effectiveness and job satisfaction of specialist nurses. Results: The overall empowerment of ICU specialist nurses was 3.37 ±0.68. In the 6 dimensions of work efficiency, the average score of formal authorization was the lowest (3.01±0.93) and that of informal authorization was the highest (3.73±0.77). Multiple linear regression analysis showed that job satisfaction of nurses increased linearly with the increase of the scores of formal authorization and informal authorization (t=2.32, 3.78,P < 0.05). The total score of satisfaction was 55.03± 8.30. The work status dimension score was 35.16± 5.94, in the middle level limit; the work interpersonal relationship dimension score was 19.87 ± 2.82, in the high level. The work status satisfaction lagged behind the work interpersonal relationship satisfaction. Simple linear regression model analysis showed that the total score of satisfaction increased linearly with the average score of work efficiency, showing a positive linear correlation (t=9.891,P < 0.01). The regression equation was: y=27.12+8.273. Conclusions Because of the linear positive correlation between job efficacy and total score of satisfaction, nursing administrators should fully grasp the various factors affecting job efficacy in clinical management, and take targeted measures to improve the work efficiency of ICU specialist nurses, and ultimately improve the job satisfaction of nurses.

Objective: To investigate the application of clohexidine wipes in patients after liver transplantation and the effect of infection prevention. Methods: A total of 279 patients who received orthotopic liver transplantation in the first affiliated hospital of sun yat-sen university from January 2017 to December 2018 and were transferred to the intensive care department of our hospital after the surgery were selected as subjects. Among them, 145 patients who received liver transplantation between January and December 2017 were selected as the control group. From January to December, 2018, 134 patients after liver transplantation were enrolled as the intervention group, and were treated with clohexidine 2% gluconate wet wipes, and the hospital infection rate, infection rate, multiple drug-resistant bacteria infection rate, bath time consumption, and adverse reaction rate were compared between the two groups. Results: The hospital infection rate of the control group was 20.00% (29/145), the infection rate of patients was 37.93%(55/145), the infection rate of multiple drug-resistant bacteria was 25.52%(37/145), and the infection rate of the intervention group was 11.19% (15/134), 24.63% (33/134), 14.93% (20/134). The differences were statistically significant (χ²=4.065, 5.709, 4.806, P<0.05). The bath time of the control group was (16.70±1.42) minutes, and the intervention group was (14.07±1.53) minutes. Compared with the control group, the bath time of the intervention group was saved, and the difference was statistically significant (t=9.637, P<0.01).No discomfort symptoms such as disinfectant allergy were found in both groups. Conclusion The application of clohexidine 2% gluconate wet wipes in the wiping bath of patients after liver transplantation had a good effect, significantly reducing the hospital infection rate, saving the time of wiping bath.

Objective To investigate the frequency and location of cerebral microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) to understand the imaging and clinical features of the disease.Methods Cranial magnetic resonance imaging and susceptibility-weighted imaging were assessed in seven symptomatic CADASIL patients in People's Hospital of Zhengzhou University from 2014 to 2017.Imaging features and clinical significance of these patients were analyzed retrospectively.Results The seven patients were diagnosed by Notch3 gene detection.Mutations were found in exon 11 in four cases,and in exon 4 in three cases.All the seven patients with CADASIL had cerebral microbleeds,the number of which was 108 (4-36).The number of cerebral microbleeds was found to be higher in cortico-subcortical region than in any other regions.One of CADASIL patients with cerebral microbleeds had intracerebral hemorrhage located in external capsule.The patient with intracerebral hemorrhage had hypertension and multiple cerebral microbleeds.Conclusions Cerebral microbleeds are common imaging characteristics in symptomatic CADASIL,most of which locate in cortico-subcortical region.Cerebral hemorrhage is one of the clinical manifestations of CADASIL patients.

Objective To explore the expression and significance of CXCL13 in gastric mucosa of children with nodular gastritis. Methods A total of 216 pediatric patients with clinically diagnosed gastritis under gastroscopy were randomly divided into nodular group and non-nodular group according to whether there were nodular changes under endoscopy. The pathological characteristics of gastric mucosa and the expression of CXCL13/CXCR5 in gastric mucosa of all patients were evaluated. Results The infection rates of Helicobacter pylori(HP)in gastric mucosa in nodule group(n=102)and non-nodular group(n=114)were 70.59% and 42.11%, respectively; the rate of severe mononuclear cell infiltration were 74.51% and 22.81%, respectively; the proportion of neutrophil infiltration were 62.75% and 33.33%, respectively; lymph follicles occurred in 64.71% and 20.18%, respectively; and there were statistical differences between the two groups (P<0.001). Positive staining of CXCL13 and CXCR5 were found in the gastric mucosa of all HP infected patients. The percentages of positive cells of CXCL13 and CXCR5 in the gastric mucosa of the nodules group were (71.33±7.14)% and (73.54 ± 7.92)%, which were higher than those in the non-nodule group (45.88 ± 5.92)% and (50.42 ± 5.98)%, respectively, and there were statistical differences (P<0.001). Conclusions Nodular gastritis in children is mainly associated with Hp infection. The expression of CXCL13/CXCR5 is increased in gastric mucosa in children with Hp infection, especially in nodular gastritis, it may be involved in the formation of lymphoid tissue in gastric mucosa.