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BACKGROUND: The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissuesï¼contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. METHODS: To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. RESULTS: The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. CONCLUSION: In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.
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Objective: To accurately verify the pathogenicity of variants of uncertain significance (VUS) in MUT and MMACHC genes through mass spectrometry and silico analysis. Methods: This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of MMUT and MMACHC variants were analyzed using silico analysis. Results: The percentage of those carrying VUS cases was 68.15% (659/967). In the MMUT gene variant, we found that C3, C3/C2, and C3/C0 levels in those carrying the P/LP variant group were higher than those in the non-variant group (p < 0.000). The conservative scores of those carrying the P/LP variant group were >7. C3, C3/C0, and C3/C2 values of newborns carrying VUS (c.1159A>C and c.1286A>G) were significantly higher than those of the non-variant group and the remaining VUS newborns (p < 0.005). The conservative scores of c.1159A>C and c.1286A>G calculated by ConSurf analysis were 9 and 7, respectively. Unfortunately, three MMA patients with c.1159A>C died during the neonatal period; their C3, C3/C0, C3/C2, and MMA levels were significantly higher than those of the controls. Conclusion: Common variants of methylmalonic acidemia in the study population were categorized as VUS. In the neonatal period, the metabolic biomarkers of those carrying the P/LP variant group of the MUT gene were significantly higher than those in the non-variant group. If the metabolic biomarkers of those carrying VUS are also significantly increased, combined with silico analysis the VUS may be elevated to a likely pathogenic variant. The results also suggest that mass spectrometry and silico analysis may be feasible screening methods for verifying the pathogenicity of VUS in other inherited metabolic diseases.
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[This corrects the article DOI: 10.1371/journal.pone.0277324.].
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The gryllacridid genus Woznessenskia Gorochov, 2002 comprises 13 extant species from Asia, with 8 species reported from China and 5 species reported from Vietnam. A new species from Xizang, China, Woznessenskia lianhua sp. nov., is reported in this paper.
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Ortópteros , Animales , Distribución Animal , Estructuras Animales , Tamaño Corporal , Tamaño de los Órganos , ChinaRESUMEN
Bile acids (BAs) have increasingly been implicated in the onset and progression of necrotizing enterocolitis (NEC); multiple findings have demonstrated their ability to induce damage to the intestinal epithelium, thereby exacerbating disease severity. Although we previously showed that melatonin was able to treat NEC by correcting the Treg/Th17 imbalance, the modulatory effect of melatonin on BAs remains unclear. In this study, we conducted transcriptome analysis on intestinal tissues from patients with NEC and validated these findings. Subsequently, we treated mice with melatonin alone or in combination with an agonist/inhibitor of Sirtuin 1 (SIRT1) to assess faecal and serum BA levels, the expression levels of BA transporters and regulators, and the extent of intestinal injury. Our transcriptome results indicated dysregulation of BA metabolism and abnormal expression of BA transporters in patients with NEC, which were also observed in our NEC mouse model. Furthermore, exogenous BAs were found to aggravate NEC severity in mice. Notably, melatonin effectively restored the aberrant expression of BA transporters, such as apical membrane sodium-dependent bile acid transporters (ASBT), ileal bile acid-binding protein (IBABP), and organic solute transporter-alpha (OST-α), by upregulating SIRT1 expression while reducing farnesoid X receptor (FXR) acetylation, consequently leading to decreased serum and faecal BA levels and mitigated NEC severity. Thus, we propose a potential mechanism through which melatonin reduces BA levels via the SIRT1/FXR signalling axis in an NEC mouse model. Collectively, these results highlight that melatonin holds promise for reducing BA levels and represents a promising therapeutic strategy for treating NEC.
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Enterocolitis Necrotizante , Melatonina , Animales , Humanos , Ratones , Ácidos y Sales Biliares/metabolismo , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/metabolismo , Intestinos , Hígado , Melatonina/farmacología , Melatonina/uso terapéutico , Sirtuina 1/metabolismoRESUMEN
Objective To explore the effects of small incision in situ release on surgical indications,nerve conduction velocity and upper limb function in patients with carpal tunnel syndrome(CTS).Methods A total of 100 CTS patients admitted to our hospital from January 2018 to January 2022 were selected,they were randomly divided into the control group(50 cases,treated with traditional carpal tunnel release)and the observation group(50 cases,treated with small incision in situ release),the clinical data of CTS patients were collected and surgical indications,nerve conduction velocity,upper limb function and the incidence of complications were compared between the two groups.Results The total effective rate was 98.00%in the observation group and 84.00%in the control group(P<0.05).In the observation group,the length of incision was(1.65±0.29)cm,the time of opening and closing incision was(4.85±1.02)min,the hospitalization time was(3.24±0.62)d,the intraoperative blood loss was(17.88±3.53)mL,and the VAS score was(3.03±0.56)points one day after operation.The control group were(4.02±0.81)cm,(10.06±2.28)min,(7.11±1.34)d,(24.37±5.27)ml,(4.04± 0.89)points,the differences were statistically significant(P<0.05).After treatment,The thumle-wrist sensory conduction velocity of CTS patients in the study group was(46.05±8.39)m/s,the middle finger-wrist sensory conduction velocity was(45.05±8.95)m/s,the thenar muscles-wrist motor conduction velocity was(53.94±11.47)m/s,the FIM ADL score was(34.38±7.22)points,and FMA The upper limb score was(34.23±7.25)points,and the control group was(41.86±8.22)m/s,(40.88±8.28)m/s,(49.05±10.01)m/s,(27.81±6.01)points,(41.05±9.19)points.The difference between the two groups was statistically significant(P<0.05).The total incidence of complications was 4.00%in the observation group and 20.00%in the control group(P<0.05).Conclusion Small incision in situ release is effective in the treatment of CTS patients,which can improve the surgical indications and nerve conduction velocity,help patients recover upper limb function,and reduce the incidence of postoperative complications.
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Currently, the main treatments for nonfunctional parathyroid cysts (NFPC) are fluid aspiration,sclerosing injection and surgical removal. The choice of treatment method is controversial. Eight patients with NFPC who were treated by simple aspiration combined with parathyroid hormone (PTH) rapid determination in General Surgery Department of Tianjin Medical University General Hospital from Dec. 2020 to Oct. 2022 are reported to provide a reference for the choice of treatment, which can also reduce surgical pain and accidental sclerosing injury.
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ObjectiveTo observe the clinical efficacy of Tongdu Huoxue decoction in the treatment of acute lumbar disc herniation (LDH). MethodA total of 316 patients with acute LDH admitted to the orthopedic outpatient department of Hubei Provincial Hospital of Traditional Chinese Medicine and Honghu City Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were randomly divided into two groups. 156 cases in the control group (two cases with stopped follow-up) were treated with meloxicam tablets, while 153 cases in the observation group (five cases with stopped follow-up) were treated with Tongdu Huoxue decoction. Both groups were treated for three months. The clinical efficacy, McGill Pain Score Scale (SF-MPQ), Oswestry Dysfunction Index (ODI) score, and the Japanese Orthopaedic Association (JOA) scores of the two groups before and after treatment were compared. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) of the patients before and after treatment were determined by using enzyme-linked immunosorbent assay (ELISA). The NDI-092 type electromyography-evoked potential instrument was adopted to measure the motor conduction velocity and clinical efficacy of the tibial and common peroneal nerves in patients of the two groups before and after treatment, and the clinical safety of the two groups of patients was compared. ResultAfter treatment, the total effective rate in the observation group was 95.4% (146/153), significantly higher than that in the control group of 76.3% (119/156) (χ2 =23.18, P<0.05). After treatment, both groups showed significant reductions in SF-MPQ and ODI scores, as well as the levels of IL-1β, IL-6, and TNF-α (P<0.05), with the observation group showing a more significant reduction (P<0.05). Both groups showed a significant increase in JOA scores and motor conduction velocities of the tibial and common peroneal nerves after treatment (P<0.05), with the observation group showing a more significant increase (P<0.05). ConclusionTongdu Huoxue decoction can alleviate lumbar and leg pain in acute LDH, improve lumbar spine function, and suppress inflammatory reactions. It is highly safe and is worthy of clinical promotion.
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ObjectiveTo explore the possible mechanism of Osteoking (OK) on postmenopausal osteoporosis (PMOP). MethodForty adult female mice were randomly divided into a sham operation (Sham) group, osteoporosis model (OVX) group, estradiol intervention (E2) group, and OK group, with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy, and the corresponding drugs were given one week later. After 12 weeks, the body mass and uterine index of mice were measured, and the pathological changes of bone tissue and the number of osteoclasts (OCs) were determined by hematoxylin-eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Bone mineral density (BMD), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone volume fraction (BV/TV) were measured by microcomputed tomography (Micro-CT). The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α (TNF-α) and bone resorption marker C-terminal telopeptide of type Ⅰ collagen (CTX-1) were measured by enzyme linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor-kappa B p65 (NF-κB p65), phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor kappa B inhibitor alpha (IκBα), phosphorylated nuclear factor kappa B alpha (p-IκBα), nuclear factor of activated T cells 1 (NFATc1), and proto-oncogene (c-Fos) were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 (MMP-9), NFATc1, TRAP, cathepsin K (CTSK), and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the Sham group, the uterine index decreased significantly in the OVX group, and the body mass (BMI) increased significantly. The structure of bone trabeculae was completely damaged, and the number of OCs increased. BMD, Tb.N, BV/TV, and maximum load decreased, while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were up-regulated (P<0.05, P<0.01). Compared with the OVX group, the body mass of the OK and E2 groups decreased, and the uterine index increased. The bone trabeculae increased, and the number of OCs decreased. BMD, Tb.N, BV/TV, and maximum load increased, while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were decreased, and the mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were decreased (P<0.05, P<0.01). ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice, which is one of the mechanisms for treating PMOP.
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Objective:To study the feasibility of laparoscopic anatomical hepatectomy of segment VII for hepatocellular carcinoma (HCC) with dorsal-ventral combined approach.Methods:Clinical data of 23 patients with HCC undergoing laparoscopic anatomical hepatectomy of segment VII with dorsal-ventral combined approach in Jiangnan University Affiliated Hospital from December 2020 to April 2023 were retrospectively collected, including 11 males and 12 females, aged (58.5±7.9) years old. The patient's perio-perative data, postoperative complications, and follow-ups were analyzed.Results:All patients underwent the surgery successfully without conversion to laparotomy. The operation time was (286.7±63.4) min, the amount of intraoperative blood loss [ M( Q1, Q3)] was 200(150, 400) ml without blood transfusion. There were no major complications such as abdominal bleeding, bile leakage, liver failure or abdominal infection. Two cases had right pleural effusion and were managed with thoracic drainage. The patients could ambulate on postoperative day 2, and the postoperative hospital stay was (9.36±1.72) d. The diameter of the lesion was (4.38±1.42) cm. The serum level of alpha fetoprotein (AFP) three months after surgery was (3.26±0.93) ng/ml, lower than the preoperative baseline (46.75±9.43) ng/ml ( t=38.24, P=0.008). All patients showed normal serum levels of AFP and there were no tumor recurrence or metastasis during postoperative follow-ups. Conclusion:Laparoscopic anatomical hepatectomy of segment VII for HCC with dorsal-ventral combined approach is feasible and worth spreading.
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OBJECTIVE@#To explore the impacts of delayed ureteral stent removal on the quality of life (QoL) and mental health of urinary calculi postoperative patients due to the corona virus disease 2019(COVID-19) pandemic.@*METHODS@#The demographic and clinical data of patients with ureteral stent placement after urinary endoscopic lithotripsy and returned to Peking University People's Hospital for stent removal from December 2019 to June 2020 were collected. Ureteral stent symptoms questionnaire (USSQ) score and the outcome 20-item self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were collected to estimate the QoL and mental status. The USSQ consisted of 44 questions in 6 domains (including urinary symptom, physical pain, general health, work performance, sexual function, and ureteral stent related infection). For most questions in each domain, its score was a five-point Likert-type scale from 1 to 5, and a small proportion of questions was quantified by 1 to 4 or 1 to 7 scale. SAS and SDS both contained 20 questions used to assess a patient's level of anxiety and depression. Its scoring for each item was on a four-point Likert-type scale from 1 to 4. A total score (ranging from 20 to 80) was the main statistical indicator. The level of clinical anxiety and depression was quantified by using standard scores (total score multiplied by 1.25 to produce integers). And the multi-group structural equation model was constructed by analysis of moment structure (AMOS) analysis.@*RESULTS@#Overall, 71 patients were enrolled for analysis. It was found that the median duration of ureteral stent time differed significantly between the control and delayed groups for 32 (30, 33) d and 94.5 (88, 103) d, respectively. The delayed group resulted in higher scores in the USSQ multidimensional, which included urinary symptoms, general health, work performance and ureteral stent related infections. Anxiety and depression were also significantly serious in the delayed group than in the control group. A longer indwelling time of a ureteral stent could exacerbate the effects of urinary symptoms and physical pain on work performance (P=0.029 < 0.05). Among them, the patients with severe urinary symptoms leading to poor work performance were most significantly affected by prolonged ureteral stent duration time (CR=2.619>1.96).@*CONCLUSION@#Patients with delayed ureteral stent removal due to the COVID-19 had resulted in worse QoL and mental status. Stents related symptoms are more severe in patients with higher anxiety and depression degree during COVID-19. To improve the QoL and mental health of patients after urinary calculi surgery during COVID-19, it is still not recommended to prolong the stent duration time or corresponding intervention measures should be taken.
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Humanos , Calidad de Vida , Pandemias , COVID-19/epidemiología , Uréter/cirugía , Cálculos Urinarios , Dolor , Enfermedades Ureterales , Stents , Encuestas y Cuestionarios , Cálculos UreteralesRESUMEN
OBJECTIVE@#To investigate the status quo of recognition and management of renal colic among urological surgeons in China.@*METHODS@#From November 2021 to March 2022, 725 urological surgeons in China were surveyed in the form of a questionnaire, including their province, hospital grade, professional title, the number of patients with renal colic treated per week, the preferred drugs and the cognition of the disease. This study was approved by the Medical Ethics Committee of Peking University People's Hospital, and all respondents completed informed consent online.@*RESULTS@#During November 2021 and March 2022, urological surgeons across China were surveyed in the form of a questionnaire, and the reliability and validity of the questionnaire were verified before the study was carried out. In the study, 720 valid questionnaires were collected (accounting for 99.31% of the total number), in which 42.4% of the doctors' preferred drugs were non-steroidal anti-inflammatory drugs (NSAIDs), and 40.0% of the doctors' preferred antispasmodic drugs. Opioids were the first choice of 11.0% of the physicians and other treatments were preferred by 6.6% of physicians. In addition, 61.1% of the doctors thought that the mechanism of renal colic was elevated prostaglandin, 32.2% thought it was ureteral spasm, 5.0% thought it was calculi irritation, and 1.7% thought the mechanism was unclear. The doctor of the cognition of the generation mechanism of renal colic pain had a significant influence on the preferred treatment option (χ2=54.399, P < 0.001) that the "elevated prostaglandins" doctor more often preferred NSAIDs than the doctor who thought cramps and ureter stones caused renal colic (51.6% vs. 28.0%, χ2=34.356, P < 0.001;51.6% vs. 19.4%, χ2=13.759, P < 0.001). In addition, hospital class, physician title, and the number of weekly consultations by physicians influenced the choice of medications for renal colic (P < 0.05), tertiary hospitals, middle and senior professional titles and weekly patients with renal colic > 8 cases generally preferred NSAIDs.@*CONCLUSION@#There are deficiencies in the cognition and drug treatment of renal colic among urological surgeons in China. The choice of the preferred drug was related to the doctor's cognition of the disease, the grade of the hospital, the doctor's professional title and the weekly treatment volume.
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Humanos , Cólico Renal/tratamiento farmacológico , Urólogos , Pueblos del Este de Asia , Reproducibilidad de los Resultados , Antiinflamatorios no Esteroideos , Encuestas y CuestionariosRESUMEN
Objective To observe the impact of readout-segmented echo-planar imaging(RS-EPI)based on small field of view(FOV)and saturation band on image quality of orbital diffusion weighted imaging(DWI).Methods Orbital MR scanning were prospectively performed in 33 healthy subjects.T1W,RS-RPI and optimized RS-EPI(based on small FOV and saturation band)images were acquired.Imaging quality of RS-EPI and optimized RS-EPI on displaying intraorbital structures(eyeballs,optic nerve and intraconal compartment)and periorbital structures(nasal cavity,orbital gyrus,optic chiasma,pituitary and temporal lobe)were evaluated subjectively using 5-point method.The geometric parameters of eyeball,signal-to-noise ratio(SNR)and apparent diffusion coefficient(ADC)were compared between images of RS-EPI and optimized RS-EPI.Results The display of eyeball,nasal cavity,orbital gyrus,optic chiasm,pituitary and temporal lobe on optimized RS-EPI were all better than those on RS-EPI(all P<0.01),whereas no significant difference of optic nerve nor intraconal compartment was found between optimized RS-EPI and RS-EPI images(P>0.05).Deformations of eyeball volume,sphericity,surface area,3D maximum diameter,axial maximum diameter and sagittal maximum diameter of bilateral eyes on optimized RS-EPI images were all slighter than those on RS-EPI(all P<0.01),whereas no significant difference of deformations of coronal maximum diameters was found between optimized RS-EPI and RS-EPI images(P>0.05).SNR of left temporal lobe white matter and ADC of vitreous body on optimized RS-EPI images were both lower than those on RS-EPI(both P<0.01),whereas no significant difference of ADC of left temporal lobe white matter nor that of pons was found between optimized RS-EPI and RS-EPI images(P>0.05).Conclusion Optimized RS-EPI with small FOV and saturation band could be used to improve imaging quality of orbital DWI.
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Objective:To explore the relationship between metabolic score for insulin resistance (METS-IR) and chronic kidney disease (CKD) and albuminuria in the Chinese population.Methods:This cross-sectional study was conducted from January to December 2018 among residents aged 20 to 70 years in ten regions of eight provinces in China; all residents had lived in their region for more than 5 years. Various parameters were measured, included fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA 1c), blood lipids, renal function, urinary albumin/creatinine ratio (UACR), etc. Data of 5 060 subjects meeting the criteria were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml·min -1·1.73 m -2 or UACR≥30 mg/g. Albuminuria was defined as UACR≥30 mg/g. METS-IR was calculated and categorized into quartiles: Q1, METS-IR≤32.19; Q2, METS-IR 32.20-37.10; Q3, METS-IR 37.11-42.58; and Q4, METS-IR>42.58. The correlation between METS-IR and CKD and albuminuria was analyzed by binary logistic regression, and subgroup analyses were performed. Results:There were 1 266, 1 266, 1 265, and 1 263 participants included in Q1-Q4 groups, respectively. With the increase of METS-IR quartile, various parameters increased, including age, fasting blood glucose, HbA 1c, triglycerides, serum uric acid, waist circumference, body mass index, and systolic and diastolic blood pressure, and the proportion of males also increased (all P<0.05). The proportion of patients with CKD and albuminuria increased significantly with the increase in interquartile range (Q) of METS-IR (all P<0.05). Logistic regression analysis showed that for every 1-unit increment of METS-IR, the risk of CKD and albuminuria were both increased by 2% [for both: odds ratio ( OR)=1.02, 95% confidence interval ( CI) 1.01-1.03]. Compared with the lowest METS-IR group (Q1), the ORs for CKD and albuminuria in the highest METS-IR group (Q4) were 1.57 (95% CI 1.17-2.10) and 1.46 (95% CI 1.09-1.96), respectively. In the subgroup analyses, increased METS-IR was significantly associated with CKD and albuminuria among women (CKD: OR=1.62, 95% CI 1.14-2.31; albuminuria: OR=1.53, 95% CI 1.07-2.18), individuals with HbA 1c<7% ( OR=1.64, 95% CI 1.21-2.23; OR=1.55, 95% CI 1.14-2.11), individuals with eGFR≥90 ml·min -1·1.73 m -2 ( OR=1.78, 95% CI 1.27-2.49; OR=1.80, 95% CI 1.28-2.53), and the Chinese Han population ( OR=1.56, 95% CI 1.13-2.17; OR=1.41, 95% CI 1.01-1.96). Conclusions:METS-IR is significantly associated with CKD and albuminuria in a Chinese population. Furthermore, the higher the METS-IR, the higher the risk of CKD and albuminuria.
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Background/Aims@#The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. @*Methods@#The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosisrelated proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. @*Results@#CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells.miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. @*Conclusions@#CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.
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More studies show that various diseases, especially chronic non-infectious diseases, have developmental origin. Developmental origins of diseases are mainly due to gametes and early life development stage being exposed to adverse environment, resulting in abnormal modification of epigenetic and stable inheritance to the adult stage, which could make the risk of various long-term diseases of individuals high. The theory of developmental origin provides a new perspective for the occurrence and development of diseases, and also provides a theoretical basis for disease prevention. Attaching importance to maternal and child health care and life-cycle management is conducive to the prevention of developmental diseases and is of great significance to the improvement of population quality.
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Adulto , Humanos , Epigénesis Genética , Enfermedad Crónica , Enfermedades no Transmisibles/genéticaRESUMEN
Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.
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Humanos , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias del Recto/terapia , Estudios Retrospectivos , Pelvis/patología , Recurrencia , Resultado del TratamientoRESUMEN
Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
Asunto(s)
Humanos , Enfermedad de Castleman/patología , Células Plasmáticas/patología , Enfermedad Relacionada con Inmunoglobulina G4 , China , Linfadenopatía/patología , Inflamación/patología , Ganglios Linfáticos/patología , Diagnóstico Diferencial , Linfadenitis/patología , Inmunoglobulina G/metabolismoRESUMEN
Objective:To investigate the value of a nomogram predicting the outcome of intracerebral hemorrhage (ICH) based on clinical characteristics and diffusion-weighted imaging (DWI) of hyperintense lesions.Methods:A case-control study. Consecutive patients, aged 30-88(59±13) years old, with ICH were recruited at the Stroke Center of Zhengzhou People′s Hospital from January 2018 to August 2021. Patients were divided into a group with DWI lesions and a group without DWI lesions depending on whether there were DWI hyperintense lesions distant from the hematoma. Prognosis was evaluated at 90 days via the modified Rankin Scale (mRS). Univariate and multivariable logistic regression models were used to identify independent predictors of a poor ICH outcome (mRS score≥4), and a nomogram model was developed. The performance of the nomogram was validated via the area under the receiver operating characteristic curve (AUC) and a calibration chart.Results:Of the 303 patients included in the study, 24.8% presented with DWI lesions; 17.5% with asymptomatic DWI lesions and 7.3% with symptomatic DWI lesions. Poor outcomes were significantly more frequent in the group with DWI lesions than in the group without DWI lesions ( χ2=21.32, P<0.001). In multivariable regression analysis, age [odds ratio ( OR)=1.032, 95% confidence interval ( CI) 1.002-1.063, P=0.035], hematoma volume ( OR=1.050, 95% CI 1.011-1.090, P=0.012), hematoma location ( OR=3.839, 95% CI 1.248-11.805, P=0.019), DWI lesions ( OR=3.955, 95% CI 1.906-8.206, P<0.001), and baseline NIHSS scores ( OR=1.102, 95% CI 1.038-1.170, P=0.001) were independent predictors of a poor outcome. In subgroup analysis patients with asymptomatic DWI lesions had a 3-fold greater risk of a poor outcome compared to those without DWI lesions ( OR=3.135, 95% CI 1.382-7.112, P=0.006), and patients with symptomatic DWI lesions had a 7-fold greater risk of a poor outcome compared to those without DWI lesions ( OR=7.126, 95% CI 2.279-22.277, P=0.001). A nomogram model was established based on the independent predictors for a poor outcome. The AUC of the nomogram was 0.846 (95% CI 0.795-0.898), and a calibration chart indicated good consistency between values predicted by the nomogram and actual observed values. Conclusions:DWI lesions are an independent risk factor for a poor outcome in patients with ICH-particularly symptomatic DWI lesions. A nomogram model based on clinical characteristics and DWI lesions exhibited good efficacy when predicting the outcome of ICH.
RESUMEN
OBJECTIVE@#To investigate the clinicopathological characteristics of micro and mini parotid gland tumors and to provide reference for their clinical diagnosis and treatment.@*METHODS@#Patients with parotid gland tumors treated in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from December 2012 to April 2020 were selected. Relevant clinical data of the patients with tumor diameter ≤20 mm detected by preoperative CT were collected to analyze the clinicopathological characteristics and prognosis of micro and mini parotid gland tumors. And the collected data were divided into two groups with diameter 11-20 mm and diameter ≤10 mm according to tumor diameter measured by preoperative CT. The clinicopathological differences between the two groups were statistically analyzed.@*RESULTS@#A total of 2 067 patients with primary epithelial parotid gland tumors were collected, and 685 patients with tumor diameter ≤20 mm were examined by CT, accounting for 33.1%. The ratio of male to female patients with micro and mini parotid gland tumors was 1 ∶1.93, the average age was (45.3±13.8) years (12-83 years), and the median course of disease was 12 months (1 week to 30 years). Among them, 635 cases (92.7%) were benign tumors, 50 cases (7.3%) were malignant tumors, and the ratio of benign to malignant was 12.7 ∶1. The most common benign tumor was pleomorphic adenoma, and the most common malignant tumor was mucoepidermoid carcinoma. The micro and mini parotid gland tumors were divided into 11-20 mm group (n=611) and ≤10 mm group (n=74), the clinical characteristics comparison of the two groups of gender ratio, average age, course of di-sease had no statistical difference (P>0.05). In the 11-20 mm diameter group, the percentage of benign and malignant tumor was 92.8% (567/611) and 7.2% (44/611) respectively, and the ratio of benign to malignant tumors was 12.9 ∶1. In the ≤10 mm diameter group, the percentage of benign and malignant tumor was 91.9% (68/74) and 8.1% (6/74) respectively, and the ratio of benign to malignant tumors was 11.3 ∶1. There was no significant difference between the two groups (P>0.05). Fifty patients with malignant tumor were followed up for the median follow-up period of 39.5 months (1-91 months). Local recurrence occurred in 2 patients with one death. The overall 2-year survival rate was 93.7% and the 5-year survival rate was 89.3%.@*CONCLUSION@#The majority of micro and mini parotid gland tumors was benign lesion. There was a good prognosis for micro and mini parotid gland carcinoma. Early surgical treatment was recommended for micro and mini parotid gland tumors.