Social decision-making in major depressive disorder: A three-level meta-analysis.

Major Depressive Disorder (MDD) is frequently associated with social dysfunction and impaired decision-making, but its impact on social decisions remains unclear. Thus, we conducted a series of meta-analyses to examine the effects of MDD on key social decision phenomena, including trust, altruistic punishment, and cooperation. We searched Web of Science, PubMed, PsycINFO, and Embase up to December 2023, using Hedges' g to compare social decision-making between MDD patients and healthy controls (HCs). Meta-analytic results showed that MDD patients exhibited a significant reduction in trust (Hedges' g = -0.347, p < 0.001), no significant difference in altruistic punishment (Hedges' g = 0.232, p = 0.149), and an increase in cooperative behaviors (Hedges' g = 0.361, p = 0.002) compared to HCs. The moderation analysis revealed that age (p = 0.039) and region (p = 0.007) significantly moderated altruistic punishment, with older MDD patients and those from Asian and European regions having larger MDD-HC contrast than others. Regarding cooperation, moderation analysis indicated that age (p = 0.028), years of education (p = 0.054), and treatment coverage (p = 0.042) were significant moderators, indicating larger MDD-HC contrast in older, less-educated and better-treated people. These findings suggest MDD has different impacts on different social decisions, highlighting the need for fine-tuned therapeutic interventions that address these differences. The data also underscores the importance of considering demographic and treatment-related variables in managing MDD, which could inform personalized treatment strategies and improve social functionality and patient outcomes.

Natural products as glycolytic inhibitors for cervical cancer treatment: A comprehensive review.

Cervical cancer, a prevalent gynaecological malignancy, presents challenges in late-stage treatment efficacy. Aerobic glycolysis, a prominent metabolic trait in cervical cancer, emerges as a promising target for novel drug discovery. Natural products, originating from traditional medicine, represent a significant therapeutic avenue and primary source for new drug development. This review explores the regulatory mechanisms of glycolysis in cervical cancer and summarises natural compounds that inhibit aerobic glycolysis as a therapeutic strategy. The glycolytic phenotype in cervical cancer is regulated by classical molecules such as HIF-1, HPV virulence factors and specificity protein 1, which facilitate the Warburg effect in cervical cancer. Various natural products, such as artemisinin, shikonin and kaempferol, exert inhibitory effects by downregulating key glycolytic enzymes through signalling pathways such as PI3K/AKT/HIF-1α and JAK2/STAT3. Despite challenges related to drug metabolism and toxicity, these natural compounds provide novel insights and promising avenues for cervical cancer treatment.

Exosomes as Emerging Regulators of Immune Responses in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood glucose levels resulting from insulin resistance and impaired insulin secretion. Immune dysregulation-mediated chronic low-grade inflammation is a critical factor that poses a significant risk to the metabolic disorders of T2DM and its related complications. Exosomes, as small extracellular vesicles secreted by various cells, have emerged as essential regulators of intercellular communication and immune regulation. In this review, we summarize the current understanding of the role of exosomes derived from immune and nonimmune cells in modulating immune responses in T2DM by regulating immune cell functions and cytokine production. More importantly, we suggest potential strategies for the clinical applications of exosomes in T2DM management, including biomarkers for disease diagnosis and monitoring, exosome-based therapies for drug delivery vehicles, and targeted therapy for exosomes.

Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

Pseudolaric acid B triggers ferritinophagy and ferroptosis via upregulating NCOA4 in lung adenocarcinoma cells.

BACKGROUND: Ferroptosis is a novel subtype of programmed cell death caused by iron-dependent lipid peroxidation and excessive reactive oxygen species (ROS) production. Small-molecule ferroptotic drugs have the probability of selectively targeting the specific features of aggressive tumor cells. In particular, pseudolaric acid B (PAB) triggered ferroptosisin breast cancer cells. The aim of this study is to explore the antitumor effect of PAB on A549 cells and provide a theoretical basis for the further development and clinical application of PAB. METHODS: First, relevant databases were used to predict of target genes related to PAB, Then, EdU proliferation assay, colony formation and wound-healing assays were applied to calculate A549 cells proliferative abilities. Measurement of ferrous iron, lipid peroxidation, ROS, malondialdehyde (MDA) and glutathione (GSH) were utilized to explore the relevant mechanism. RESULTS: We showed that PAB decreased the viability of lung adenocarcinoma cells in vitro, which was accompanied by abnormally elevated levels of intracellular ferrous iron and overproduction of lipid reactive oxidate species (L-ROS). In turn, deferoxamine (DFO) significantly rescued PAB-induced lipid peroxidation. PAB also improved the intracellular labile iron pool by promoting ferritin autophagy via the upregulation of the nuclear receptor coactivator 4 (NCOA4). Moreover, silencing of NCOA4 alleviated PAB-inducedferroptotic death and reduced the levels of intracellular ferrous iron. CONCLUSIONS: In summary, PAB-triggered ferroptosis in lung adenocarcinoma cells by enhancing ferritinophagy. thus, PAB is a potential therapeutic agent for lung adenocarcinoma.

Palliative care and Chinese medicine in a centenarian with primary hepatocellular carcinoma and 27-month follow-up: A case report.

The number of centenarians with cancer is increasing as the global population ages. The diagnosis and treatment for centenarians with tumor sometimes are specific, and there are currently less appropriate guidelines as references. We report a 104-year-old man with asymptomatic primary liver cancer (PLC) whose family decided to receive conservative and palliative care. The patient has been followed up for 27 months. He has been mainly received Chinese herbal medicine (CHM), nutritional support and thymalfasin injection intermittently, etc. During the 27-month follow-up, the patient has showed good compliance and tolerance without any complications of the tumor. Conclusion: Individualized palliative care and complementary medicine, based on multidisciplinary evaluation, traditional Chinese medicine, consultation with patients and their families about treatment options, etc., may help improve the life quality of centenarians with end-stage tumors.

Loss of spines in the prelimbic cortex is detrimental to working memory in mice with early-life adversity.

Adverse experiences in early life can shape neuronal structures and synaptic function in multiple brain regions, leading to deficits of distinct cognitive functions later in life. Focusing on the pyramidal cells of the prelimbic cortex (PrL), a main subregion of the medial prefrontal cortex, the impact of early-life adversity (ELA) was investigated in a well-established animal model generated by changing the rearing environment during postnatal days 2 to 9 (P2-P9), a sensitive developmental period. ELA has enduring detrimental impacts on the dendritic spines of PrL pyramidal cells, which is most apparent in a spatially circumscribed region. Specifically, ELA affects both thin and mushroom-type spines, and ELA-provoked loss of spines is observed on selective dendritic segments of PrL pyramidal cells in layers II-III and V-VI. Reduced postsynaptic puncta represented by postsynaptic density protein-95 (PSD-95), but not synaptophysin-labelled presynaptic puncta, in ELA mice supports the selective loss of spines in the PrL. Correlation analysis indicates that loss of spines and postsynaptic puncta in the PrL contributes to the poor spatial working memory of ELA mice, and thin spines may play a major role in working memory performance. To further understand whether loss of spines affects glutamatergic transmission, AMPA- and NMDA-receptor-mediated synaptic currents (EPSCs) were recorded in a group of Thy1-expressing PrL pyramidal cells. ELA mice exhibited a depressed glutamatergic transmission, which is accompanied with a decreased expression of GluR1 and NR1 subunits in the PrL. Finally, upregulating the activation of Thy1-expressing PrL pyramidal cells via excitatory DREADDs can efficiently improve the working memory performance of ELA mice in a T-maze-based task, indicating the potential of a chemogenetic approach in restoring ELA-provoked memory deficits.

Ellagic acid inhibits the formation of hypertrophic scars by suppressing TGF-ß/Smad signaling pathway activity.

Hypertrophic scar (HS) is a benign fibroproliferative skin disease, which lacks the ideal treatment and drugs. Ellagic acid (EA) is a natural polyphenol that prevents fibroblasts from proliferating and migrating. This study aimed to determine the role of EA in HS formation and its possible mechanism by in vitro experiments. HS fibroblasts (HSFs) and normal fibroblasts (NFs) were separated from HS tissue and normal skin tissue, respectively. HSFs were treated with 10 and 50 µM EA to assess their effect on HS formation. In particular, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and scratch assay were used to detect the viability and migration ability of HSFs. Quantitative reverse transcriptase real-time polymerase chain reaction was used to measure the mRNA expression level of basic fibroblast growth factor (bFGF), extracellular matrix (ECM)-related gene collagen-I (COL-I), and fibronectin 1 (FN1) in HSFs. Finally, Western blot was utilized to measure the expression level of TGF-ß/Smad signaling pathway-related proteins in HSFs. The viability of HSFs was significantly increased compared with NFs. 10 and 50 µM EA treatment markedly inhibition the cell viability and migration of HSFs. EA treatment upregulated the bFGF expression level and downregulated the COL-I and FN1 expression level in HSFs. In addition, p-Smad2, p-Smad3, and transforming growth factor (TGF)-ß1 expression levels as well as p-Smad2/Smad2 and p-Smad3/Smad3 ratios remarkably decreased in HSFs after EA treatment. EA inhibited the formation of HSs by suppressing the viability and migration of HSFs and ECM deposition as well as by preventing the activation of TGF-ß/Smad signaling.

Comparison and fusion prediction model for lung adenocarcinoma with micropapillary and solid pattern using clinicoradiographic, radiomics and deep learning features.

To investigate whether the combination scheme of deep learning score (DL-score) and radiomics can improve preoperative diagnosis in the presence of micropapillary/solid (MPP/SOL) patterns in lung adenocarcinoma (ADC). A retrospective cohort of 514 confirmed pathologically lung ADC in 512 patients after surgery was enrolled. The clinicoradiographic model (model 1) and radiomics model (model 2) were developed with logistic regression. The deep learning model (model 3) was constructed based on the deep learning score (DL-score). The combine model (model 4) was based on DL-score and R-score and clinicoradiographic variables. The performance of these models was evaluated with area under the receiver operating characteristic curve (AUC) and compared using DeLong's test internally and externally. The prediction nomogram was plotted, and clinical utility depicted with decision curve. The performance of model 1, model 2, model 3 and model 4 was supported by AUCs of 0.848, 0.896, 0.906, 0.921 in the Internal validation set, that of 0.700, 0.801, 0.730, 0.827 in external validation set, respectively. These models existed statistical significance in internal validation (model 4 vs model 3, P = 0.016; model 4 vs model 1, P = 0.009, respectively) and external validation (model 4 vs model 2, P = 0.036; model 4 vs model 3, P = 0.047; model 4 vs model 1, P = 0.016, respectively). The decision curve analysis (DCA) demonstrated that model 4 predicting the lung ADC with MPP/SOL structure would be more beneficial than the model 1and model 3 but comparable with the model 2. The combined model can improve preoperative diagnosis in the presence of MPP/SOL pattern in lung ADC in clinical practice.

MiR-210-5p promotes the differentiation of human induced pluripotent stem cells into dopaminergic neural precursors by targeting SMAD4 and SUFU and treats parkinsonian rats.

The differentiation of human induced pluripotent stem cells (hiPSCs) into functional dopaminergic neural precursors is the basis of cell therapy for Parkinson's disease (PD). However, the use of small molecule inhibitors/activators in the differentiation of hiPSCs in vitro leads to cell death and low differentiation efficiency. Moreover, the mechanism of differentiation remains unclear. MiR-210-5p was increased during hiPSCs differentiation. Whether it promotes hiPSCs differentiation and transplantation needs further study. Here, we overexpressed miR-210-5p in hiPSCs to study its roles and mechanisms. We found that miR-210-5p promoted the differentiation of hiPSCs into dopaminergic neural precursors and reduced the expression of SMAD4 and SUFU meanwhile. Luciferase assays showed that miR-210-5p binded to SMAD4 and SUFU, which are key molecules in the key signals (TGF-ß and SHH) of hiPSCs differentiation. Furthermore, in the effect evaluation of cell transplantation into parkinsonian rats, the degree of behavioral recovery and the growth of transplanted cells in the group overexpressed miR-210-5p were similar to those in the positive group with all small molecule inhibitors/activators. Therefore, we conclude that miR-210-5p promotes the differentiation of hiPSCs into dopaminergic neural precursors by targeting SMAD4 and SUFU. In the therapeutic evaluation of cell transplantation, miR-210-5p can replace the use of corresponding small molecule inhibitors/activators to reduce cell death. This study provides an experimental basis and a new target for the miRNA-modified differentiation of hiPSCs and cell transplantation in clinical treatment of PD in the future.

Botulinum neurotoxin A ameliorates depressive-like behavior in a reserpine-induced Parkinson's disease mouse model via suppressing hippocampal microglial engulfment and neuroinflammation.

Depression is one of the common non-motor symptoms of Parkinson's disease (PD). In the clinic, botulinum neurotoxin A (BoNT/A) has been used to treat depression. In this study, we investigated the mechanisms underlying the anti-depressive effect of BoNT/A in a PD mouse model. Mice were administered reserpine (3 µg/mL in the drinking water) for 10 weeks. From the 10th week, BoNT/A (10 U·kg-1·d-1) was injected into the cheek for 3 consecutive days. We showed that chronic administration of reserpine produced the behavioral phenotypes of depression and neurochemical changes in the substantia nigra pars compacta (SNpc) and striatum. BoNT/A treatment significantly ameliorated the depressive-like behaviors, but did not improve TH activity in SNpc of reserpine-treated mice. We demonstrated that BoNT/A treatment reversed reserpine-induced complement and microglia activation in the hippocampal CA1 region. Furthermore, BoNT/A treatment significantly attenuated the microglial engulfment of presynaptic synapses, thus ameliorating the apparent synapse and spine loss in the hippocampus in the reserpine-treated mice. Moreover, BoNT/A treatment suppressed microglia-mediated expression of pro-inflammatory cytokines TNF-α and IL-1ß in reserpine-treated mice. In addition, we showed that BoNT/A (0.1 U/mL) ameliorated reserpine-induced complement and microglia activation in mouse BV2 microglial cells in vitro. We conclude that BoNT/A ameliorates depressive-like behavior in a reserpine-induced PD mouse model through reversing the synapse loss mediated by classical complement induced-microglial engulfment as well as alleviating microglia-mediated proinflammatory responses. BoNT/A ameliorates depressive-like behavior, and reverses synapse loss mediated by classical complement pathway-initiated microglia engulfment as well as alleviates microglia-mediated proinflammatory response in the reserpine-induced Parkinson's disease mouse model.

[Clinical effect of Corail femoral prosthesis with different offset in total hip arthroplasty].

OBJECTIVE: To explore the early clinical efficacy of primary total hip arthroplasty(THA) with Corail standard stems (KS type) and high offset stems (KHO type), by analyzing the postoperative radiographic parameters of different offset of femoral components with Corail stem which has a neck-shaft angle of 135 ° in unilateral primary THA, by comparing the measurement results on both sides and analyzing the reconstruction of the postoperative femoral offset and the hip joint function recovery. METHODS: A retrospective analysis was made of 186 patients with unilateral hip joint lesions who underwent the first total hip arthroplasty with Johnson & Johnson Corail prostheses from January 2015 to June 2017. According to the use of femoral prostheses with different eccentricities during the operation, the patients were divided into high eccentricity group and standard eccentricity group. In the high eccentricity group, there were 52 cases of Corail high eccentricity prosthesis(KHO type), including 20 females and 32 males;aged 21 to 71 years old with an average of(50.6±13.2) years;body mass index(BMI) was (26.0±4.1) kg/m2. The standard eccentricity group included 134 Corail standard femoral stem prostheses(KS type), 57 females and 77 males;aged 18 to 77 years old with an average of (47.3±14.0) years;BMI was (25.3±3.5) kg/m2. The abduction arm, femoral eccentricity, acetabular eccentricity and the length difference of lower limbs were measured on the postoperatively positive X-ray film of the hip joint. Harris score and related complications were recorded before and after the operation, and the stability of the prosthesis was analyzed. RESULTS: There were significant differences in femoral eccentricity, joint eccentricity and abduction arm between the affected side and the healthy side in the high eccentricity group(P<0.05). There were significant differences in femoral eccentricity and acetabular eccentricity between the affected side and the healthy side in the standard eccentricity group(P<0.05). There were significant differences in combined eccentricity, abduction arm and length of lower limbs between two groups(P<0.05). In the high eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and joint eccentricity(r=0.633, P<0.001;r=0.384, P=0.005;r=0.690, P<0.001). The same results were also obtained in the healthy side(r=0.688, P<0.001;r=0.574, P<0.001;r=0.765, P<0.001). In the standard eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and combined eccentricity(r=0.734, P<0.001;r=0.418, P<0.001;r=0.749, P<0.001). The same results were also obtained in the healthy side(r=0.775, P<0.001;r=0.397, P<0.001;r=0.773, P<0.001). The difference of the length of both lower limbs was significantly correlated with the difference of bilateral joint eccentricity and bilateral abduction arm (r=0.376, P=0.006;r=-0.346, P=0.012). There was no significant correlation between the difference of the length of both lower limbs and the difference of bilateral joint eccentricity and bilateral abduction arm (r=-0.009, P=0.919;r=-0.036, P=0.682). There was no significant difference in Harris score between two groups at the last follow-up(P>0.05). At the last follow-up, Trendelenburg was negative in all patients in both groups, and the prostheses were stable. CONCLUSION: Both Corail standard stem and high offset stem may be effectively reconstruct the femoral offset, reconstruct the anatomical structure and biomechanics of the hip joint, and maintain the length of lower limbs and the stability of the hip joint in the unilateral primary total hip arthroplasty. Although the offset of the femur was not reconstructed normally in some cases, the stability of the components and postoperative function were not affected.

Early patellar tendon rupture after total knee arthroplasty: A direct repair method.

BACKGROUND: Patellar tendon rupture after total knee arthroplasty (TKA) is a catastrophic complication. Although the occurrence of this injury is rare, it can lead to significant dysfunction for the patient and is very tricky to deal with. There has been no standard treatment for early patella tendon rupture after TKA, and long-term follow-up data are lacking. AIM: To introduce a direct repair method for early patella tendon rupture following TKA and determine the clinical outcomes and complications of this method. METHODS: During the period of 2008 to 2021, 3265 consecutive TKAs were retrospectively reviewed. Twelve patients developed early patellar tendon rupture postoperatively and were treated by a direct repair method. Mean follow-up was 5.7 years. Demographic, operative, and clinical data were collected. The clinical outcomes were assessed using the Western Ontario and McMaster Universities (WOMAC) score, the Hospital for Special Surgery (HSS) score, knee range of motion, extensor lag, and surgical complications. Descriptive statistics and paired t test were employed to analyze the data. RESULTS: For all 12 patients who underwent direct repair for early patellar tendon rupture, 3 patients failed: One (8.3%) for infection and two (17.6%) for re-fracture. The two patients with re-fracture both underwent reoperation to reconstruct the extensor mechanism and the patient with infection underwent revision surgery. The range of motion was 109.2° ± 10.6° preoperatively to 87.9° ± 11° postoperatively, mean extensor lag was 21° at follow-up, and mean WOMAC and HSS scores were 65.8 ± 30.9 and 60.3 ± 21.7 points, respectively. CONCLUSION: This direct repair method of early patellar tendon rupture is not an ideal therapy. It is actually ineffective for the recovery of knee joint function in patients, and is still associated with severe knee extension lag and high complication rates. Compared with the outcomes of other repair methods mentioned in the literature, this direct repair method shows poor clinical outcomes.

Preclinical reserpine models recapitulating motor and non-motor features of Parkinson's disease: Roles of epigenetic upregulation of alpha-synuclein and autophagy impairment.

Reserpine is an effective drug for the clinical treatment of hypertension. It also induces Parkinson's disease (PD)-like symptoms in humans and animals possible through the inhibition of monoamine vesicular transporters, thus decreasing the levels of monoamine neurotransmitters in the brain. However, the precise mechanisms remain unclear. Herein, we aimed to develop a preclinical reserpine model recapitulating the non-motor and motor symptoms of PD and investigate the underlying potential cellular mechanisms. Incubation of reserpine induced apoptosis, led to the accumulation of intracellular reactive oxygen species (ROS), lowered DNA methylation of alpha-synuclein gene, resulted in alpha-synuclein protein deposition, and elevated the ratio of LC3-II/LC3-Ⅰ and p62 in cultured SH-SY5Y cells. Feeding reserpine dose-dependently shortened the lifespan and caused impairment of motor functions in male and female Drosophila. Moreover, long-term oral administration of reserpine led to multiple motor and non-motor symptoms, including constipation, pain hypersensitivity, olfactory impairment, and depression-like behaviors in mice. The mechanistic studies showed that chronic reserpine exposure caused hypomethylation of the alpha-synuclein gene and up-regulated its expression and elevated the ratio of LC3-II/LC3-Ⅰ and expression of p62 in the substantia nigra of mice. Thus, we established preclinical animal models using reserpine to recapitulate the motor and non-motor symptoms of PD. Chronic reserpine exposure epigenetically elevated the levels of alpha-synuclein expression possible by lowering the DNA methylation status and inducing autophagic impairment in vitro and in vivo.

Different squatting positions after total knee arthroplasty: A retrospective study.

BACKGROUND: Total knee arthroplasty (TKA) has been shown to improve quality of life and reduce pain. High-flexion activities such as squatting, kneeling, and floor transfers are mainly listed as demanding tasks. Among them, squatting is an important position. AIM: To provide a new squat position classification and evaluate the different squatting positions of a series of patients after primary TKA. METHODS: From May 2018 to October 2019, we retrospectively reviewed 154 video recordings of the squatting-related motions of patients after TKA. Among the included patients, 119 were women and 35 were men. Their mean age at the index surgery was 61.4 years (range, 30 to 77). RESULTS: The median follow-up was 12 mo (range, 6 to 156 mo). We classified those squatting-related motions into three major variations according to squatting depth: Half squat, parallel squat, and deep squat. The angles of hip flexion, knee flexion, and ankle dorsiflexion were measured in the screenshots captured from the videos at the moment of squatting nadir. A total of 26 patients were classified as half squats, 75 as parallel squats, and 53 as deep squats. The angles of hip flexion, knee flexion, and ankle dorsiflexion all differed significantly among the three squatting positions (P < 0.001). In the parallel squat group, the mean knee flexion angle (°) was 116.5 (SD, 8.1; range, 97 to 137). In the deep squat group, the mean knee flexion angle (°) was 132.5 (SD, 9.3; range, 116 to 158). CONCLUSION: Among the three squatting positions, deep squat showed the highest hip, knee, and ankle flexion angles, followed by the parallel squat. With the improvement of squatting ability, the patient's postoperative satisfaction rate was also significantly enhanced. However, the different squatting abilities of the patients cannot be effectively distinguished from the scoring results (P > 0.05). Our squatting position classification offers a pragmatic approach to evaluating patients' squatting ability after TKA.

Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome.

BACKGROUND: The chronic visceral subtype of acid sphingomyelinase deficiency, commonly known as Niemann Pick disease type B (NPDB), is a relatively rare autosomal recessive genetic disorder that is caused by mutations in the SMPD1 gene. NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS), as it lacks specific clinical characteristics. This makes its diagnosis difficult. CASE PRESENTATION: Here, we report a case of NPDB with SBH that was misdiagnosed as BCS for three years. A 20-year-old female with abdominal distension, hepatosplenomegaly, and haematological anomalies was initially diagnosed with BCS based on her imaging finding of a thin hepatic vein and rapid blood flow at the confluence of the hepatic vein and inferior vena cava. Her bone marrow cytology found sea-blue histiocytes. Liver biopsy showed foamy cytoplasm in hepatocytes surrounded by numerous Kupffer cells. Sequencing analysis of the SMPD1 gene led to the finding of two missense mutations in the heterozygous state: C.829 T > C (p.Trp277Arg) in exon 2 (novel) and c.1805G > A (p.Arg602His) in exon 6 (already described). These findings established the diagnosis of NPDB. CONCLUSION: The patient presented with hepatosplenomegaly, haematological anomalies, and dyslipidaemia. Thus, NPDB should be considered following the exclusion of related diseases. The diagnosis of NPDB was suspected by clinical symptoms and routine laboratory tests and was confirmed by liver biopsy and gene sequencing. The novel mutation c.829 T > C in exon 2 of the SMPD1 gene has never been reported and needs to be further investigated.

[Application of high offset Corail femoral stem prosthesis in unilateral primary total hip arthroplasty].

OBJECTIVE: To investigate the application of high offset femoral stem prosthesis in primary total hip arthroplasty. METHODS: From January 2015 to June 2017, 51 patients with unilateral hip diseases who underwent primary total hip arthroplasty with Corail high offset femoral stem prosthesis(KHO type) were selected for retrospective study, including 20 females and 31 males;the age ranged from 21 to 71 years old with an average of(50.8±13.3) years old. The abduction arm, femoral offset, acetabular offset and the length of lower limbs were measured on the positive X-ray film of hip joint after operation. Harris scores before and after operation and related complications were recorded, and the stability of prosthesis was analyzed. RESULTS: The femoral offset, combined offset and abduction arm of the affected side were significantly greater than those of the healthy side(P<0.05). There was no significant difference in acetabular offset between the affected side and the healthy side (P>0.05). The femoral offset of 17 hips (33.3%) was reconstructed normally, of which 15 cases (88.2%) had equal length of both lower limbs. The femoral offset of 34 hips (66.7%) was greater than that of the healthy side, and 34 cases (100%) had equal length of both lower limbs. All 51 patients were followed up for(42.3±7.3) months. The Harris score increased from 38.0±7.6 before operation to 92.1±3.1 at the final follow-up(P<0.001). CONCLUSION: Although the high offset Corail prosthesis can not normally reconstruct the femoral offset in unilateral primary total hip arthroplasty, it does not affect the reconstruction of the length of lower limbs and the stability of the prosthesis.

Serum DSG2 as a potential biomarker for diagnosis of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma.

BACKGROUND: Exploration of serum biomarkers for early detection of upper gastrointestinal cancer is required. Here, we aimed to evaluate the diagnostic potential of serum desmoglein-2 (DSG2) in patients with esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA). METHODS: Serum DSG2 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 459 participants including 151 patients with ESCC, 96 with EJA, and 212 healthy controls. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS: Levels of serum DSG2 were significantly higher in patients with ESCC and EJA than those in healthy controls (P<0.001). Detection of serum DSG2 demonstrated an area under the ROC curve (AUC) value of 0.724, sensitivity of 38.1%, and specificity of 84.8% for the diagnosis of ESCC in the training cohort, and AUC 0.736, sensitivity 58.2%, and specificity 84.7% in the validation cohort. For diagnosis of EJA, measurement of DSG2 provided a sensitivity of 29.2%, a specificity of 90.2%, and AUC of 0.698. Similar results were observed for the diagnosis of early-stage ESCC (AUC 0.715 and 0.722, sensitivity 36.3 and 50%, and specificity 84.8 and 84.7%, for training and validation cohorts, respectively) and early-stage EJA (AUC 0.704, sensitivity 44.4%, and specificity 86.9%). Analysis of clinical data indicated that DSG2 levels were significantly associated with patient age and histological grade in ESCC (P<0.05). CONCLUSION: Serum DSG2 may be a diagnostic biomarker for ESCC and EJA.

A study on the marine ecological security assessment of Guangdong-Hong Kong-Macao Great Bay Area.

The construction of world-class Bay makes the marine ecology in Guangdong-Hong Kong-Macao Great Bay Area in risk. Based on the DPSIR index framework, Lotka-Volterra symbiosis model is applied to calculate symbiosis degree between coastal socio-economic system and marine ecosystem in 9 coastal cities. It is found that the marine ecological pressure in this area have not been reversed in recent 20 years. Most cities are in the stage that socio-economic development and marine ecological damage coexist. In Shenzhen, Guangzhou, Dongguan and Zhongshan, the damaged marine ecology has begun to restrain the further expansion of economy and society. The massive population agglomeration in Hong Kong, Macao and other places has caused serious marine ecological stress. It is urgent to improve the marine ecological security by cultivating ecological industrial system and industrial clusters, establishing a land-sea ecological restoration, promoting joint-protection and co-governance across different administrative regions.

Cucurbitacin E inhibits cellular proliferation and induces apoptosis in melanoma by suppressing HSDL2 expression.

BACKGROUND: Melanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma. METHODS: HSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma. RESULTS: HSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo. CONCLUSION: HSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.