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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(6): 608-614, 2024 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-38901994

ABSTRACT

Objective: To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Methods: Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores. Results: Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46-63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44-58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1-2 in 246 patients (50.5%) and 3-4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8-16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7-133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8-16, and >16 were 85.1%, 80.5%, and 66.4%, respectively (P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408-0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559-4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer (P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62-0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49-0.60). The two scores differed significantly in accuracy (Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion: The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Male , Female , Retrospective Studies , Middle Aged , Disease-Free Survival , Aged , Prognosis , Neoplasm Recurrence, Local , Adult , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Rectum/surgery , Chemoradiotherapy , Proportional Hazards Models
3.
Zhonghua Er Ke Za Zhi ; 61(11): 989-994, 2023 Nov 02.
Article in Chinese | MEDLINE | ID: mdl-37899338

ABSTRACT

Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.


Subject(s)
Brain Diseases , Posterior Leukoencephalopathy Syndrome , Seizures, Febrile , Status Epilepticus , Male , Female , Child , Humans , Infant , Child, Preschool , Posterior Leukoencephalopathy Syndrome/complications , Seizures/diagnostic imaging , Seizures/etiology , Brain Diseases/diagnostic imaging , Seizures, Febrile/diagnostic imaging
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(10): 993-1001, 2023 Oct 12.
Article in Chinese | MEDLINE | ID: mdl-37752041

ABSTRACT

Objective: To study the effect and mechanism of post-ischemic treatment of nalmefene in alleviating the lung ischemia-reperfusion injury by inhibiting ferroptosis through activation of the Sirt 1/Nrf 2/HO-1 axis. Methods: A total of 60 rats were randomly divided into six groups equally (n=10): the sham group, the model group(I/R), the nalmefene group, the nalmefene+EX527 group, the nalmefene+ML385 group, the nalmefene+Fe-citrate group (nalmefene+Fe group). The sham group without drug treatment was not treated with ischemia-reperfusion. The pulmonary ischemia-reperfusion model was established by occlusion of the left pulmonary hilum in the model group without drug treatment. After ischemic treatment, the nalmefene group was injected with nalmefene (15 µg/kg) via the tail vein at 5 minutes before reperfusion. The nalmefene+EX527 group, the nalmefene+ML385 group, and the nalmefene+Fe group were injected intraperitoneally with EX527 (5 mg/kg), ML385 (30 mg/kg), Fe-citrate(15 mg/kg), respectively, 2 h before moulding and then injected with nalmefene (15 µg/kg) via the tail vein at 5 minutes before reperfusion. All rats were sacrificed three hours after reperfusion, and the specimens from the upper lobe of the left lung tissue were preserved. The degree of lung tissue injury and the wet/dry weight ratio were assessed in each group of rats. Fe 2+, MDA, TNF-α, and IL-6 content, GSH activity and the expression levels of Sirt1, Nrf2, HO-1, ACSL4 and GPX4 were determined. Results: Compared with the sham group, the wet/dry weight ratio, lung tissue injury score, ACSL 4 expression level, Fe 2+, TNF-α, IL-6 and MDA content, Sirt 1, Nrf 2, HO-1 messenger RNA and protein expression levels were significantly increased (P<0.01), while GPX 4 expression level and GSH activity were significantly decreased in the model group (P<0.01). Compared with the model group, wet/dry weight ratio, lung tissue injury score, ACSL 4 expression level, Fe 2+, TNF-α, IL-6, and MDA content decreased significantly (P<0.01), Nrf 2, HO-1 messenger RNA and protein, GPX 4 expression, and GSH activity were significantly increased in the nalmefene group and the nalmefene+EX527 group (P<0.01). Sirt 1 messenger RNA and protein expression increased significantly in the nalmefene (P<0.01) and the nalmefene+EX527 groups (P>0.05). In the nalmefene+ML385 group, the wet/dry weight ratio, lung tissue injury score, TNF-α and IL-6 content were decreased significantly (P<0.01), while Sirt 1 messenger RNA and protein expression levels were significantly increased (P<0.01), but there were no significant changes in Nrf 2, HO-1 messenger RNA and protein expression levels, ACSL 4 and GPX 4 expression levels, Fe 2+, MDA content, and GSH activity (P>0.05). In the nalmefene+Fe group, wet/dry weight ratio, lung-injury score, TNF-α, IL-6, MDA content were decreased significantly (P<0.01), messenger RNA and protein expression levels of Sirt 1, Nrf 2, HO-1, and GSH activity were increased significantly (P<0.01), but there were no significant changes in Fe 2+content, ACSL 4 and GPX 4 expression levels (P>0.05). Compared with the nalmefene group, in the nalmefene+EX527 group, the nalmefene+ML385 group and the nalmefene+Fe group, wet/dry weight ratio, lung tissue damage score, ACSL 4 expression level, TNF-α, IL-6 and MDA content were significantly increased (P<0.01), the expression level of GPX 4 and GSH activity were significantly decreased (P<0.01). The expression levels of Sirt 1, Nrf 2, HO-1 messenger RNA and protein were significantly decreased in the nalmefene+EX527 group (P<0.01). The expression levels of Nrf 2, HO-1 messenger RNA and protein decreased significantly in the namemefene+ML385 group (P<0.01), but there was no significant change in Sirt 1 messenger RNA and protein expression level (P>0.05). Sirt 1, Nrf 2, HO-1 messenger RNA-protein expression levels did not change significantly in the nalmefene+Fe group (P>0.05). Conclusion: Post-ischemic treatment with nalmefene hydrochloride may alleviate pulmonary ischemia-reperfusion injury by inhibiting ferroptosis through activation of the Sirt 1/Nrf 2/HO-1 axis.


Subject(s)
Ferroptosis , Lung Injury , Reperfusion Injury , Animals , Rats , Citrates , Citric Acid , Interleukin-6 , Ischemia , Lung , NF-E2-Related Factor 2 , Reperfusion Injury/drug therapy , RNA, Messenger , Sirtuin 1 , Tumor Necrosis Factor-alpha
5.
Ecotoxicol Environ Saf ; 264: 115416, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37647801

ABSTRACT

Cadmium (Cd) is a common contaminant in aquatic environments. However, little is known about the mechanisms underlying Cd toxicity in the freshwater snail Cipangopaludina cathayensis (Heude, 1890). This study to investigate the toxic effects of Cd on the standard metabolism, antioxidant activities, immune function, and hepatopancreas transcriptome profiles of C. cathayensis. C. cathayensis was exposed to 0.25, 0.5, 1.0, or 1.5 mg/L Cd for 3 h, with results showing that Cd significantly inhibited oxygen consumption and ammonia excretion and disrupted the respiratory metabolism of C. cathayensis. In addition, the O:N ratio dropped below 7, indicating that C. cathayensis may rely exclusively on proteins as an energy source under Cd stress. To understand how Cd impacts the antioxidant activities, immune function, and transcriptional profiles, C. cathayensis were exposed to 0.5 (low exposure, L14) or 1.5 (high exposure, H14) mg/L Cd for 14 days. Our results indicate that Cd exposure leads to oxidative stress and immunosuppression, with the latter effect being larger for exposure to higher Cd concentrations. A total of 2172 differentially expressed genes (DEGs) were identified by transcriptome analysis of the hepatopancreas, of which 885 were upregulated and 1287 were downregulated. Gene ontology and KEGG analyses revealed that the DEGs in the H14 group are enriched for energy generation terms and the "oxidative phosphorylation" pathway, respectively. Therefore, up-regulation of energy metabolism may be an adaptive strategy under Cd stress. Moreover, several genes involved in antioxidant activity were downregulated, whereas genes related to reactive oxygen species generation were upregulated. In addition, many immunity-related genes were identified within the DEGs, indicating that Cd toxicity may affect immune defense. Further, DEGs in the H14 group were enriched for disease-associated pathways. Taken together, our results indicate that Cd exposure leads to metabolic disorders, oxidative stress, and immunosuppression and thus may potentially contribute to disease outbreaks.


Subject(s)
Antioxidants , Transcriptome , Animals , Antioxidants/metabolism , Cadmium/metabolism , Hepatopancreas/metabolism , Immunity
6.
Ultramicroscopy ; 253: 113771, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37301082

ABSTRACT

Ultrafast-optical-pump - structural-probe measurements, including ultrafast electron and x-ray scattering, provide direct experimental access to the fundamental timescales of atomic motion, and are thus foundational techniques for studying matter out of equilibrium. High-performance detectors are needed in scattering experiments to obtain maximum scientific value from every probe particle. We deploy a hybrid pixel array direct electron detector to perform ultrafast electron diffraction experiments on a WSe2/MoSe2 2D heterobilayer, resolving the weak features of diffuse scattering and moiré superlattice structure without saturating the zero order peak. Enabled by the detector's high frame rate, we show that a chopping technique provides diffraction difference images with signal-to-noise at the shot noise limit. Finally, we demonstrate that a fast detector frame rate coupled with a high repetition rate probe can provide continuous time resolution from femtoseconds to seconds, enabling us to perform a scanning ultrafast electron diffraction experiment that maps thermal transport in WSe2/MoSe2 and resolves distinct diffusion mechanisms in space and time.

10.
Cancer Radiother ; 26(8): 1054-1063, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36036359

ABSTRACT

PURPOSE: In order to explore whether partial breast irradiation can replace hypofractionated whole breast irradiation and whether the former two are superior to conventional fractionated whole breast irradiation, we conducted a network meta-analysis based on the data from the latest randomized controlled trials to evaluate the efficacy of these radiotherapy modalities. MATERIAL AND METHODS: Data from eligible studies were analyzed to determine the published events for ipsilateral breast tumor recurrence, distant metastasis, total deaths, and non-breast cancer-related deaths. In the case of low or high heterogeneity, the fixed-effect or random-effect model was used for statistical analysis respectively. NMA was performed by using the node-splitting model for two-category data among three radiotherapies based on a Bayesian method. RESULTS: A total of 23,418 patients were included in 16 studies. For ipsilateral breast tumor recurrence, both pairwise (OR=1.9; CI95%: 1.2 -2.8; p<0.05) and indirect (OR=1.7; CI95%: 1.2 -2.4; p<0.05) comparison of three radiotherapies by network meta-analysis showed that conventional fractionated whole breast irradiation was significantly better than partial breast irradiation. Indirect comparison of three radiotherapies by network meta-analysis showed that hypofractionated whole breast irradiation was significantly better than partial breast irradiation (OR=1.6; CI95%: 1.0 -2.5; p<0.05). Network and paired meta-analyses found no significant differences in other endpoints among the three radiotherapies. CONCLUSION: Overall, this network meta-analysis showed that partial breast irradiation was related to the increase of ipsilateral breast tumor recurrence compared with hypofractionated or conventional fractionated whole breast irradiation in patients with early-stage breast cancer.


Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Humans , Female , Neoplasm Recurrence, Local/surgery , Network Meta-Analysis , Bayes Theorem , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Radiotherapy, Adjuvant
11.
Struct Dyn ; 9(2): 024302, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35350376

ABSTRACT

We report the design and performance of a time-resolved electron diffraction apparatus capable of producing intense bunches with simultaneously single digit micrometer probe size, long coherence length, and 200 fs rms time resolution. We measure the 5d (peak) beam brightness at the sample location in micro-diffraction mode to be 7 × 10 13 A / m 2 rad 2 . To generate high brightness electron bunches, the system employs high efficiency, low emittance semiconductor photocathodes driven with a wavelength near the photoemission threshold at a repetition rate up to 250 kHz. We characterize spatial, temporal, and reciprocal space resolution of the apparatus. We perform proof-of-principle measurements of ultrafast heating in single crystal Au samples and compare experimental results with simulations that account for the effects of multiple scattering.

12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(1): 177-181, 2022 Feb 18.
Article in Chinese | MEDLINE | ID: mdl-35165487

ABSTRACT

OBJECTIVE: Thoracoabdominal aortic aneurysm is one of the most challenging aortic diseases. Open surgical repair remains constrained with considerable perioperative morbidity and mortality. The emergence of a hybrid approach utilizing visceral debranching with endovascular aneurysm repair has brought an alternative for high-risk patients. This study aimed to compare the short- and long-term outcomes between hybrid and open repairs in the treatment of thoracoabdominal aortic aneurysms. METHODS: In this retrospectively observational study, patients with thoracoabdominal aortic aneurysm treated in a single center between January 2008 and December 2019 were reviewed, of whom 11 patients with hybrid repair, and 18 patients with open repair were identified. Demographic characteristic, operative data, perioperative morbidity and mortality, freedom from reintervention, and long-term survival were compared between the two groups. RESULTS: In the hybrid repair group, the patients with dissection aneurysm, preoperative combined renal insufficiency, and American Society of Anesthesiologists (ASA) score of 3 or more were significantly overwhelming than in the open repair group. The operation time of debranching hybrid repair was (445±85) min, and the intraoperative blood loss was (955±599) mL. There were 2 cases of complications in the early 30 days after surgery, without paraplegia, and 1 case died. The 30-day complication rate was 18.2%, and the 30-day mortality was 9.1%. The operation time of the patients with open repair was (560±245) min, and the intraoperative blood loss was (6 100±4 536) mL. Twelve patients had complications in the early 30 days after surgery, including 1 paraplegia and 4 deaths within 30 days. The 30-day complication rate was 66.7%, and the 30-day mortality was 22.2%. The bleeding volume in hybrid repair was significantly reduced compared with open repair (P < 0.001). Besides, the incidence of 30-day complications in hybrid surgery was significantly reduced (P=0.011). During the follow-up period, there were 4 reinterventions and 3 deaths in hybrid repair group. The 1-year, 5-year, and 10-year all-cause survival rates were 72%, 54%, and 29%, respectively. In open repair group, reintervention was performed in 1 case and 5 cases died, and the 1-year, 5-year, and 10-year all-cause survival rates were 81%, 71%, and 35%, respectively. There was no significant difference between hybrid repair and open repair in all-cause survival and aneurysm-specific survival. CONCLUSION: Hybrid approach utilizing visceral debranching with endovascular aneurysm repair is a safe and effective surgical method for high-risk patients with thoracoabdominal aortic aneurysms. The incidence of early postoperative complications and mortality is significantly reduced compared with traditional surgery, but the efficacy in the medium and long term still needs to be improved.


Subject(s)
Aortic Aneurysm, Abdominal , Aortic Aneurysm, Thoracic , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Humans , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
13.
15.
Zhonghua Yi Xue Za Zhi ; 101(47): 3890-3896, 2021 Dec 21.
Article in Chinese | MEDLINE | ID: mdl-34905890

ABSTRACT

Objective: To evaluate different protocol optimization strategies for temporal bone between10 µm otology CT and multi-slice CT (MSCT). Methods: Ten adult skull specimens (20-sides temporal bones) were prospectively enrolled. From October to November 2020, the temporal bones were scanned under four different imaging conditions using 10 µm otology CT (90 kV, 120 mAs; 90 kV, 140 mAs; 100 kV, 120 mAs; 100 kV, 140 mAs) and MSCT (120 kV, 220 mAs; 120 kV, 310 mAs; 140 kV, 160 mAs; 140 kV, 220 mAs), respectively. The image quality was subjectively scored using 5-grade scores, and the contrast noise ratio (CNR) of the image was measured. The absorbed dose of tissues and organs under different imaging conditions was measured by thermoluminescence dosimeter, and the effective dose was calculated. The figure of merit (FOM) is defined as the ratio of the square of the mean CNR to the effective dose. χ2 test was used to compare the difference of subjective scores of different scanning parameter groups, and paired t test was used to analyze and compare the difference of image CNR of different scanning parameter groups. The image quality, radiation dose and FOM of the combination of recommended parameters of the two devices were analyzed and compared. Results: For 10 µm otology CT, under 100 kV condition, the CNR of 140 mAs group was better than that of 120 mAs group (11.27±1.85 vs 10.26±1.38, P<0.001). There was no significant difference in subjective scores between the two groups [5.00 (4.00, 5.00) vs 5.00 (4.25, 5.00), P=0.264]. For MSCT, under 120 kV condition, the subjective scores and CNR of 310 mAs group were better than those of 220 mAs at 120 kV [4.00(3.00, 4.00) vs 3.00(3.00, 3.00),P=0.002;5.24±0.62 vs 4.60±0.62,P<0.001]. According to the principle of image quality-radiation dose optimization, the combination of 100 kV with 120 mAs and 120 kV with 310 mAs are recommended for 10 µm otology CT and MSCT, respectively. The subjective scores and CNR of 10 µm otology CT images were better than those of MSCT (5.00 (4.25, 5.00) vs 4.00 (3.00, 4.00), 10.26±1.38 vs 5.48±0.22, P<0.001). The effective dose was 1/3 of that of MSCT (82.99 µSv vs 252.56 µSv), and the FOM was 11.16 times of that of MSCT (1 268.44 mSv-1 vs 113.71 mSv-1). Conclusion: The temporal bone image quality of newly developed 10 µm otology CT is significantly better than that of MSCT, and its effective dose is lower than that of MSCT, which has more accurate and safer application potential.


Subject(s)
Otolaryngology , Tomography, X-Ray Computed , Radiation Dosage , Temporal Bone/diagnostic imaging
16.
Eur Rev Med Pharmacol Sci ; 25(17): 5349-5354, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34533789

ABSTRACT

Salidroside, a kind of natural herb, has the advantages of a wide range of anti-tumor activities with low toxicity and high efficiency. A large number of studies have shown that salidroside can inhibit the proliferation of tumors in different ways and achieve the goal of treating tumors. After summary and analysis of the recent research on anti-tumor mechanisms of salidroside, it can be concluded that salidroside could suppress cancer proliferation by blocking cell cycle, promoting cell differentiation, inducing cell apoptosis or autophagy, and regulating the signal pathways of cancer cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Glucosides/pharmacology , Neoplasms/drug therapy , Phenols/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Cell Differentiation/drug effects , Humans , Signal Transduction/drug effects
17.
Zhonghua Er Ke Za Zhi ; 59(1): 42-46, 2021 Jan 02.
Article in Chinese | MEDLINE | ID: mdl-33397003

ABSTRACT

Objective: To investigate the clinical characteristics and genetic features of congenital myasthenic syndrome (CMS) related to SLC25A1 gene variant. Methods: The clinical data of two SLC25A1 gene variant related CMS patients treated at the Children's Hospital of Fudan University between January 2015 and June 2019 were analyzed retrospectively. A literature search with "SLC25A1" and "congenital myasthenic syndrome" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to June 2020). The clinical characteristics and genetic features of congenital myasthenic syndrome related to SLC25A1 gene variant were summarized. Results: Two patients were all males, aged 9 years and 2 years respectively and the onset age was in infancy. In addition to typical CMS symptoms (fatigable muscular weakness, including bilateral ptosis, strabismus, masticatory weakness, low voice and limb weakness), the two patients both had developmental delay along with metabolic abnormalities (elevated urinary 2-ketoglutarate (2-KG), elevated lactic acid levels or 2-hydroxyglutaric aciduria). Trio whole-exome sequencing (WES) revealed two novel pathogenic variants of SLC25A1(c.628C>T, p.R210X; c.145G>A, p.V49M) in case 1 and (c.145G>A, p.V49M; microdeletion) in case 2. After literature search, 15 cases in 3 English articles were found, which made up the complete case data of 17 patients (including these 2 cases). Seventeen patients had very early onset with the age of 2 years. Mild intellectual disability was recorded in 9 patients, and mild developmental delay was observed in one patient. 5 SLC25A1 gene variants (three missense, one nonsense and one microdeletion) were identified in these cases. Twelve patients from 6 pedigrees harbored one same variant (c.740G>A, p.R247Q) and two cases had the other variant (c.145G>A, p.V49M). Conclusions: Patients diagnosed with SLC25A1 related CMS have very early onset, and most of them have intellectual disability or developmental delay. Part of patients had metabolic abnormalities. The variants (c.740G>A, p.R247Q and c.145G>A, p.V49M) are recurrent.


Subject(s)
Brain Diseases, Metabolic, Inborn , Myasthenic Syndromes, Congenital , Organic Anion Transporters , Child , Child, Preschool , China , Humans , Male , Mitochondrial Proteins/genetics , Mutation , Myasthenic Syndromes, Congenital/genetics , Pedigree , Retrospective Studies
18.
Theriogenology ; 159: 69-76, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33113446

ABSTRACT

Polyunsaturated fatty acids (PUFAs) are essential for mammalian testis development and sperm function. However, PUFAs that are contained in linseed oil are easily oxidized in the diet and biohydrogenated in the rumen. In this study, we investigated the effect of linseed as a source of PUFAs on the antioxidant capacity and testis development in Hu lamb. Seventy-five 3-month-old lambs were randomly assigned to three groups. Within each treatment group, 25 lambs were allocated to five pens (five lambs per pen). The lambs in the control group were fed a control diet without linseed for 42 days from D22 to D63. Group I (BS28) was fed a control diet from D22 to D35 and 8% linseed diet from D36 to D63. Group II (BS42) was fed an 8% linseed diet for 42 days from D22 to D63. After 63-day feeding trial, all lambs except the heaviest and lightest in each pen were humanely slaughtered and investigated. Results revealed that feeding linseed did not affect the body weight, scrotal circumference, and testis weight, whereas feeding linseed for 42 days increased the epididymis weight (37.85 ± 1.61 g vs. 32.09 ± 1.06 g, P < 0.05) compared with the control group. Feeding lambs with linseed for 42 days also significantly upregulated the expression of antioxidative (glutathione peroxidase 4 and copper-zinc superoxide dismutase), steroidogenesis (3ß-hydroxysteroid dehydrogenase and steroid acute regulatory protein), and PUFA metabolism-related genes (fatty acid desaturase 2 and elongation of very long-chain fatty acid protein 2) and proliferating cell nuclear antigen mRNA (P < 0.05). It also increased the relative expression of mitochondrial DNA (P < 0.05), total antioxidant capacity (0.230 ± 0.019 mmol/mgprot vs. 0.175 ± 0.011 mmol/mgprot, P < 0.05), and superoxide dismutase (1661.467 ± 147.117 U/mgprot vs. 1158.891 ± 98.850 U/mgprot, P < 0.05) in testicular tissue but decreased the cholesterol concentration (0.331 ± 0.073 mmol/mgprot vs. 0.671 ± 0.092 mmol/mgprot, P < 0.05) compared with the control group. Therefore, feeding lambs with linseed for 42 days stimulated seminiferous tubule development and increased the number of Sertoli cells (20.71 ± 0.89 vs. 17.6 ± 0.73, P < 0.05), epididymal cauda lumina diameter (638.26 ± 22.32 µm vs. 444.41 ± 34.80 µm, P < 0.05), and the number of sperm in the epididymal cauda (68.91 ± 7.06 × 108/g vs. 36.61 ± 7.50 × 108/g). All these results suggested that feeding linseed in the early reproductive development stage of lambs upregulated the expression of antioxidative, steroidogenesis, and PUFA metabolism-related genes; increased the antioxidant capacity in lamb's testis; and contributed to testis development and spermatogenesis.


Subject(s)
Flax , Linseed Oil , Animal Feed/analysis , Animals , Antioxidants , China , Diet/veterinary , Epididymis , Male , Sheep , Spermatozoa , Testis
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(11): 1927-1932, 2020 Nov 10.
Article in Chinese | MEDLINE | ID: mdl-33297663

ABSTRACT

Norovirus are now recognized as one of the main pathogens causing acute gastroenteritis in both developed and developing countries. However, norovirus are easily mutated and recombined, and have many genotypes. In early studies, norovirus were amplified and identified by amino acid sequence of VP1 region. It was found that norovirus were easily mutated and recombined in or near the overlapping regions of polymerase and capsid. A two regions genotyping method was positively proposed internationally. Depending on the 2 times standard deviation standard method for two regions identification, norovirus polymerase regions can be divided into 10 gene groups and 76 genotypes including 2 tentative gene groups and 16 tentative genotypes. The VP1 region can be divided into 12 gene groups and 53 genotypes including 2 tentative gene groups and 5 tentative genotypes. However, the tentative gene groups and genotypes need to be further identified and reclassified. In this article, characteristics of norovirus sequences, principles of different genotyping methods, methods of sequence amplification, on-line genotyping tools and the latest studies in norovirus genotypes are reviewed and introduced.


Subject(s)
Norovirus , Genotype , Humans , Norovirus/genetics
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