Hemodynamics in nutcracker syndrome: implications for diagnosis.

BACKGROUND: Nutcracker syndrome is a disease characterized by complex symptoms, making its diagnosis challenging and often delayed, often resulting in a painful experience for the patients. OBJECTIVE: This study aimed to investigate the pathogenesis of nutcracker syndrome through the perspective of hemodynamics by simulating blood flow with varying compression degrees of the left renal vein. METHODS: 3D patient-specific vascular models of the abdominal aorta, superior mesenteric artery and left renal vein were constructed based on CT images of patients suspected of having nutcracker syndrome. A hemodynamic simulation was then conducted using computational fluid dynamics to identify the correlation between alterations in hemodynamic parameters and varying degrees of compression. RESULTS: The study indicated the presence of an evident gradient in velocity distribution over the left renal vein with relatively high degrees of stenosis (α ≤ 50°), with maximum velocity in the central region of the stenosis. Additionally, when the compression degree of the left renal vein increases, the pressure distribution of the left renal vein presents an increasing number of gradient layers. Furthermore, the wall shear stress shows a correlation with the variation of blood flow velocity, i.e., the increase of wall shear stress correlates with the acceleration of the blood flow velocity. CONCLUSIONS: Using computational fluid dynamics as a non-invasive instrument to obtain the hemodynamic characteristics of nutcracker syndrome is feasible and could provide insights into the pathological mechanisms of the nutcracker syndrome supporting clinicians in diagnosis.

Mechanisms of mental illness anti-stigma messaging matter: Leveraging mental health communication inequities among Latinx populations to understand what works and what we can do better.

BACKGROUND: Since 1950, public communication about the neurobiological-psychosocial basis of mental illness from the diathesis-stress model has promoted reception to treatment yet violent/dangerous stereotypes have increased during this period. Moreover, public mental health communication efforts have predominantly diffused in English-language media, excluding Spanish/Latinx media and its consumers from these efforts. To inform future mental health communication strategies, this study leverages high versus low diffusion of public mental health communication across English and Spanish/Latinx media to examine public mental health communication effects on stigma and treatment beliefs via neurobiological-psychosocial beliefs. METHODS: A quota sample of 2058 U.S.-based Latinx residents ages 13-86 with diverse language/cultural media preferences was recruited to self-complete a survey about mental health information acquisition in 2021. Assessments ascertained frequency of Spanish/Latinx and English media use and mental health content scanning and seeking (α = 0.86-0.94); and items from the General Social Survey about mental illness neurobiological-psychosocial causal beliefs (α = 0.72)-genetics, brain chemistry, environment, stress; treatment beliefs-mental illness improves with treatment or on its own; and stigma beliefs-violent/dangerous and bad character stereotypes and unwillingness to socialize with a person with mental illness. Structural equation models estimated total, direct, and indirect effects of Spanish/Latinx and English media exposures on treatment and stigma beliefs via neurobiological-psychosocial beliefs, net individual/family factors. RESULTS: Spanish/Latinx media reduced, while English media increased, neurobiological-psychosocial beliefs (p < 0.01). Neurobiological-psychosocial beliefs, in turn, increased treatment and stigma beliefs (p < 0.01), simultaneously. Indirect pathways were also significant (p < 0.05). Proportion mediated on treatment beliefs was one-third for Spanish/Latinx and two-thirds for English media. Proportion mediated on stigma beliefs for all media exposures averaged ≥1. CONCLUSIONS: While consumers of Spanish/Latinx media report lower neurobiological-psychosocial knowledge that impedes treatment beliefs, consumers of English media report greater neurobiological-psychosocial and treatment knowledge and, consequently, more stigma. Innovation in public mental health communication is needed to counter stigma and health inequity.

Quantitative estimation of dust transport in the desert region of northwest China by plutonium isotopes.

Dust is an important source of atmospheric pollution, and quantitative estimation of desert dust transport is crucial for air pollution control. In this study, five typical sandy soil profiles in the Tengger Desert were collected and analyzed for 239,240Pu concentration and 240Pu/239Pu atomic ratios in order to identify the source of 239,240Pu in this area and explore the sedimentary characteristics of dust in different profiles. The results revealed that the concentrations of 239,240Pu in the soil profiles were between 0.002 and 0.443 mBq/g with an exception of the deep layer soil at one site. The measured atomic ratios of 240Pu/239Pu are at the global atmospheric fallout level with a mean of 0.184 ± 0.020, indicating that global fallout is the dominant source of plutonium in this region. The total inventories of 239,240Pu in the reference sites in this area were estimated to be 39.2-44.6 Bq/m2, this is in agreement with the value from the global fallout of atmospheric nuclear weapon tests at the similar latitude (30-40 °N: 42 Bq/m2). The estimated erosion rate in the erosion profile utilizing soil erosion intensity mode is 2491 t/km2/yr and the soil erosion depth is 9.86 cm, While, the stacking rate of the accumulation profile is 1383 t/km2/yr, and the depth of accumulation is estimated to be 5.48 cm. The difference between the erosion and accumulation profiles indicated that approximately 1107 t/km2/yr of dust was exported from the Gobi landform area of the Tengger Desert, which might be transported long distance in the downwind direction.

Generation of an induced pluripotent stem cell line (SJTUGHi003-A) from a patient with Sorsby fundus dystrophy carrying c.484G>A mutation in TIMP3 gene.

Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disorder with macular dystrophy and severe visual loss. Mutations in TIMP3 gene has been related to SFD with mechanisms unclear. We have successfully reprogrammed the peripheral blood mononuclear cells (PBMCs) from an SFD patient carrying c.484G>A mutation in TIMP3 gene to induced pluripotent stem cells (iPSCs) and characterized their pluripotency and genetic stability. This line may serve as a useful tool to explore the role of TIMP3 in SFD pathogenesis.

Palladium-catalyzed alkynylation of allylic gem-difluorides.

Herein, a palladium-catalyzed regioselective alkynylation, esterification, and amination of allylic gem-difluorides via C-F bond activation/transmetallation/ß-C elimination or nucleophilic attack has been achieved. This innovative protocol showcases an extensive substrate range and operates efficiently under mild reaction conditions, resulting in high product yields and Z-selectivity. Particularly noteworthy is its exceptional tolerance towards a wide array of functional groups. This developed methodology provides effective and convenient routes to access a diverse array of essential fluorinated enynes, esters and amines.

Two laser-assisted hatching methods of embryos in ART: a systematic review and meta-analysis.

BACKGROUND: Laser-assisted hatching (LAH) stands as the predominant technique for removing the zona pellucida (ZP) in embryos, primarily consisting of two methods: drilling laser-assisted hatching (D-LAH) and thinning laser-assisted hatching (T-LAH). Presently, both methods have limitations, and their comparative efficacy for embryo implantation and clinical pregnancy remains uncertain. AIM: Evaluate the impact of D-LAH and T-LAH on clinical pregnancy rates within assisted reproductive technology (ART). METHODS: We systematically searched electronic databases including PubMed, Web of Science, and Cochrane Library until July 20, 2022. This study encompassed observational studies and randomized controlled trials (RCTs). A 95% confidence interval (CI) was utilized for assessing the risk ratio (RR) of pregnancy outcomes. The level of heterogeneity was measured using I2 statistics, considering a value exceeding 50% as indicative of substantial heterogeneity. RESULTS: The meta-analysis scrutinized 9 studies involving 2405 clinical pregnancies from D-LAH and 2239 from T-LAH. Findings suggested no considerable variation in the clinical pregnancy rates between the two techniques (RR = 0.93, 95% CI: 0.79-1.10, I2 = 71%, P = 0.41). Subgroup analyses also revealed no substantial differences. However, D-LAH exhibited a notably higher occurrence of singleton pregnancies compared to T-LAH (RR = 2.28, 95% CI: 1.08-4.82, I2 = 89%, P = 0.03). There were no noteworthy distinctions observed in other secondary outcomes encompassing implantation rate, multiple pregnancies, ongoing pregnancy, miscarriage, premature birth, and live birth. CONCLUSION: Both the primary findings and subgroup analyses showed no marked variance in clinical pregnancy rates between D-LAH and T-LAH. Therefore, patients with varying conditions should select their preferred LAH technique after assessing their individual situation. However, due to the restricted number of studies involved, accurately gauging the influence of these laser techniques on clinical outcomes is challenging, necessitating further RCTs and high-quality studies to enhance the success rate of ART. TRIAL REGISTRATION: PROSPERO: CRD42022347066.

A sequential light-harvesting system with thermosensitive colorimetric emission in both aqueous solution and hydrogel.

Inspired by natural photosynthetic systems that feature both sequential energy transfer and temperature response, we herein report an artificial thermosensitive sequential light-harvesting system (LHS) based on an amphiphilic molecule TPEO. It self-assembles into fluorescent nanoparticles in water and shows tunable LCST behavior. By loading ESY as the first acceptor and NiR as the second acceptor into the nanoparticles, an artificial LHS with two-step FRET was successfully constructed. Interestingly, the system exhibits thermosensitive colorimetric fluorescence in both aqueous solution and hydrogel by taking advantage of a combination of LCST and sequential FRET.

The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro.

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

Accessing Benzoazepine Derivatives via Photoinduced Radical Relay Formal [5 + 2] Reaction of Amide/Alkyne Enabled by Palladium Catalysis.

A novel class of alkyne-tethered amides facilitates an unprecedented photoinduced palladium-catalyzed radical relay formal [5 + 2] reaction. This innovative strategy allows for the rapid construction of diverse fused benzoazepine structures, yielding structurally novel and compelling compounds. With a broad substrate scope and excellent functional group tolerance, the methodology synthesizes biologically active compounds. Notably, the resulting tricyclic benzo[b]azepines offer diversification opportunities through simple transformations. DFT calculations elucidate a seven-membered ring closure mechanism involving the alkenyl radical and Pd(I) rebound alongside a concerted metalation-deprotonation (CMD) process.

Risk Factors for Postoperative Cognitive Decline After Orthopedic Surgery in Elderly Chinese Patients: A Retrospective Cohort Study.

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.

Nitrous Oxide to Reduce Wound Care-Related Pain in Adults: A Systematic Review and Meta-Analysis.

Significance: As an essential procedure, wound care comes with acute pain, which is short but high in intensity, causing patients to fear and affecting subsequent treatment. Nitrous oxide (N2O) is used to relieve pain related to wound care; however, evidence regarding its application is conflicting. Thus, this systematic review and meta-analysis was performed to evaluate the efficacy of N2O in wound care-related pain. Recent Advances: Randomized controlled trials that investigated the effect of N2O in adults undergoing wound care were systematically searched from PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov up to February 2023. The primary outcome was the pain score. Secondary outcomes included patients' satisfaction and side effects. Critical Issues: Through screening the 265 identified articles, seven and six studies were finally included in the systematic review and meta-analysis, respectively. Pooled analysis suggested that there was no significant difference in reducing wound care-related pain between the N2O group and the control group (mean difference [MD], -0.02, 95% confidence interval [CI], -1.46, 1.42; p = 0.98, I2 = 96%). Subgroup analyses indicated that there was a significant difference in favor of N2O for burns, not for ulcers, and N2O was superior to oxygen and similar to topical or intravenous anesthesia. There was no significant difference in patients' satisfaction or the incidence of side effects between groups. Future Directions: This review suggests that N2O might be effective for pain management in patients undergoing wound care. Caution must be taken when interpreting these results due to the high risk of biased methods in the included studies.

Reconstructing atmospheric 129I deposition over 170 years with the varved sediment in the Sihailongwan Maar Lake, northeast China.

Long-term deposition of atmospheric radioactive iodine-129 (129I) is important for assessing the impact of human nuclear activities (HNAs), but still not well understood in East Asia. In this study, we quantitatively reconstructed the deposition history of airborne 129I using varved sediment from Sihailongwan Maar Lake (SHLW) in northeast China. Our results revealed significant increases in 129I concentrations and 129I/127I atomic ratios since the 1950s, indicating the influence of HNAs on the environment and marking the onset of the Anthropocene. The variation of 129I in the investigated site can be primarily attributed to the global fallout of ANWT as well as nuclear fuel reprocessing in Europe, Russia and the USA. Notably, neither the Chernobyl nor the Fukushima nuclear accidents have had any discernable impact on the SHLW Lake. Over the past 170 years (1846-2021), the reconstructed fluxes indicate a rapid increase in 129I deposition from the early 1950s until the 1970s followed by dramatic changes thereafter. The measured 129I fluxes range between (1.26-349) × 109 atoms m-2 yr-1 in the SHLW Lake, which are consistent with similar latitude zones across East Asia, but differ significantly from those observed in high-elevation glaciers within the Northern Hemisphere due to prevailing atmospheric circulation patterns. The total 129I inventory was calculated to be 11.9 × 1012 atoms m-2, with natural and anthropogenic 129I accounting for 2.86 % and 97.1 %, respectively, suggesting an overwhelming artificial contribution. The reconstructed fluxes and inventory of atmospheric 129I deposition quantitatively distinguish the natural and artificial contributions, and provide a novel insight into the historical environmental impact of HNAs in East Asia and the characteristics of the Anthropocene.

Oxalic acid secretion alleviates saline-alkali stress in alfalfa by improving photosynthetic characteristics and antioxidant activity.

Saline-alkali stress significantly affects the growth and yield of alfalfa (Medicago sativa L.). Organic acid secretion is crucial in alleviating abiotic stress-induced damage in plants. In this study, we evaluated the contents of the major organic acids secreted by the roots of tolerant (ZD) and sensitive (LYL) varieties of alfalfa under saline-alkali stress and investigated the effects of these organic acids on the growth, and physiological functions of alfalfa. Our results indicated that the oxalic acid (OA) content was the highest among the organic acids secreted from alfalfa roots under saline-alkali stress, and oxalic acid content was the most significantly different between the two varieties, ZD and LYL, compared to the contents of the other organic acids. Oxalic acid alleviated the inhibition of alfalfa growth caused by saline-alkali stress, improved photosynthetic characteristics, reduced the accumulation of reactive oxygen species, and increased the activity of antioxidant enzymes and content of osmoregulatory substances. Furthermore, oxalic acid resulted in significantly increased expression of genes involved in photosynthesis and antioxidant system in alfalfa under saline-alkali stress. This study revealed the effects of oxalic acid secreted by the root system on stress-related physiological processes, providing valuable insights into the functions of root secretions in plant saline-alkali resistance.

Neoadjuvant therapy in renal cell carcinoma with tumor thrombus: A systematic review and meta-analysis.

To evaluate the efficacy, feasibility and safety of neoadjuvant therapy (NAT) for renal cell carcinoma with tumor thrombus (RCC-TT) in terms of response, perioperative and oncological outcomes, and compare the results between neoadjuvant and non-neoadjuvant groups. Overall, 29 single-arm studies and 5 cohort studies were included. Of the 204 patients undergoing NAT, 16.2% were level I, 35.3% level II, 24.0% level III and 18.6% level IV thrombus. Most of patients underwent preoperative targeted therapy, immunotherapy-based combination therapy was applied in 5.4% patients. The total reduction rate of thrombus level was 29.4%. NAT is associated with a shorter operative time, less blood loss (p<0.05 for both). Rate of complications and oncological outcomes were similar between two groups. Overall, 32.1% (34/106) ≥ grade 3 adverse events occurred in patients undergoing NAT. Neoadjuvant therapy is safe and feasible with acceptable perioperative outcomes in RCC-TT.

Antagonistic activity and mechanism of Bacillus subtilis CG-6 suppression of root rot and growth promotion in Alfalfa.

Root rot is a common disease, that severely affects the yield and quality of alfalfa. Biocontrol is widely used to control plant diseases caused by pathogenic fungi, however, biocontrol strains for alfalfa root rot are very limited. In this study, a Bacillus subtilis CG-6 strain with a significant biocontrol effect on alfalfa root rot was isolated. CG-6 secretes antibacterial enzymes and siderophore, phosphate solubilization and indoleacetic acid (IAA). The inhibition rate of strain CG-6 against Fusarium oxysporum was 87.33%, and it showed broad-spectrum antifungal activity. Inoculation with CG-6 significantly reduced the incidence of alfalfa root rot, the control effect of greenhouse cultivation reached 58.12%, and CG-6 treatment significantly increased alfalfa plant height, root length, fresh weight, and dry weight. The treatment with CG-6 significantly increased the levels of antioxidant enzymes (catalase, peroxidase, superoxide dismutase, and lipoxygenase) in alfalfa leaves by 15.52%-34.03%. Defensive enzymes (chitinase and ß-1,3-glucanase) increased by 24.37% and 28.08%, respectively. The expression levels of regulatory enzyme genes (MsCAT, MsPOD, MsCu, Zn-SOD1, MsCu, Zn-SOD2, MsCu, Zn-SOD3, and MsLOX2) and systemic resistance genes (MsPR1, MsPDF1.2, and MsVSP2) increased by 0.50-2.85 fold, which were higher than those in the pathogen treatment group. Therefore, CG-6 could be used as a potential strain to develop biopesticides against alfalfa root rot.

Assessment of land use change of ecological green wedge and cooling island effect: A case study of Wuhan, China.

The construction of urban ecological green wedges, which can mitigate the heat island effect through cooling and ventilation effects, is an important way to enhance the adaptation of cities to climate change. Dynamic monitoring and periodic assessment of both the conservation status and cooling effect of ecological green wedges is a key to ensure the heat mitigation benefits. Based on multi-source remote sensing data, we systematically analyzed the land use changes of six ecological green wedges in Wuhan in 2013 and 2020 using the methods of Markov transfer matrix, land use dynamics, and comprehensive index of land use degree, and evaluated the changes in surface temperature of the ecological green wedges and their cooling island effect. Results showed that the ecological green wedges in Wuhan generally had a large amount of construction land encroaching on ecological land from 2013 to 2020, with the water decreased the most. With the continuous deterioration of ecological green wedges, their land surface temperatures showed rising trends, together with significant weakening trends in cooling island effects. Among all the six wedges, the Dadonghu, Tangxun, and Wuhu exhibited relatively better ecological conservation, slighter land use change and lower overall development degree. Qinglinghu and Houguanhu demonstrated average levels of conservation. Fuhe experienced the most severe change under the significant influence of the westward policy of Wuhan City, with the proportion of water decreasing by 7.1%, warming up by 3.00 ℃, and the largest reduction in cooling distance for the cooling island effect, amounting to about 210 m. The results provided scientific evidence for the urban heat island mitigation-oriented planning and management of ecological green wedges for Wuhan City.

Physiological and Transcriptomic Analyses Reveal the Mechanisms Underlying Methyl Jasmonate-Induced Mannitol Stress Resistance in Banana.

Exogenous methyl jasmonate (MeJA) application has shown promising effects on plant defense under diverse abiotic stresses. However, the mechanisms underlying MeJA-induced stress resistance in bananas are unclear. Therefore, in this study, we treated banana plants with 100 µM MeJA before inducing osmotic stress using mannitol. Plant phenotype and antioxidant enzyme activity results demonstrated that MeJA improved osmotic stress resistance in banana plants. Thereafter, to explore the molecular mechanisms underlying MeJA-induced osmotic stress resistance in banana seedlings, we conducted high-throughput RNA sequencing (RNA-seq) using leaf and root samples of "Brazilian" banana seedlings treated with MeJA for 0 h and 8 h. RNA-seq analysis showed that MeJA treatment upregulated 1506 (leaf) and 3341 (root) genes and downregulated 1768 (leaf) and 4625 (root) genes. Then, we performed gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses on the differentially expressed genes. We noted that linoleic acid metabolism was enriched in both root and leaf samples, and the genes of this pathway exhibited different expression patterns; 9S-LOX genes were highly induced by MeJA in the leaves, whereas 13S-LOX genes were highly induced in the roots. We also identified the promoters of these genes, as the differences in response elements may contribute to tissue-specific gene expression in response to MeJA application in banana seedlings. Overall, the findings of this study provide insights into the mechanisms underlying abiotic stress resistance in banana that may aid in the improvement of banana varieties relying on molecular breeding.

Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank.

Objective: The occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers. Methods: A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships. Results: After adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration <10 years or CRP<1.3mg/L or males, IMDs had no effect on incident ALS. Interpretation: Our study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.

Case report: A novel variant (H49N) in Myelin Protein Zero gene is responsible for a patient with Charcot-Marie-Tooth disease.

This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.

Establishment of the induced pluripotent stem cell line SJTUGHi002-A from a CNGA1-related recessive retinitis pigmentosa patient.

Retinitis pigmentosa (RP) is the most common inherited retinal diseases, characterized by photoreceptor cell death and retinal pigment epithelial atrophy. Mutations in cyclic nucleotide gated channel subunit alpha 1 (CNGA1) have been reported to cause retinitis pigmentosa. Here, we established the human induced pluripotent stem cell line (iPSC) SJTUGHi002-A, generated from peripheral blood mononuclear cells of a 36-year-old male RP patient, who carried a homozygous frameshift variant in CNGA1 gene (c.265delC; p.L89Ffs*4). The cell line can serve as a patient-derived disease model for exploring the pathogenesis and drug development of CNGA1-RP.