Risk of hepatocellular carcinoma occurrence after antiviral therapy for patients with chronic hepatitis C Infection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of hepatocellular carcinoma (HCC) occurrence following antiviral therapy in patients with chronic hepatitis C (CHC) remains unclear. The current study aims to compare: (1) the HCC occurrence rate following sustained virological response (SVR) versus non-response (NR); (2) the HCC occurrence rate following direct-acting antiviral (DAA) therapy versus interferon (IFN)-based therapy, and (3) the HCC occurrence rate in SVR patients with or without cirrhosis. METHODS: A search was performed for articles published between January 2017 and July 2022. Studies were included if they assessed HCC occurrence rate in CHC patients following anti-HCV therapy. Random effects meta-analysis was used to synthesize the results from individual studies. RESULTS: A total of 23 studies including 29,395 patients (IFN-based = 6, DAA = 17; prospective = 10, retrospective = 13) were included in the review. HCC occurrence was significantly lower in CHC with SVR (1.54 per 100 person-years (py, 95% CI 1.52, 1.57) than those in non-responders (7.80 py, 95% CI 7.61, 7.99). Stratified by HCV treatment regimens, HCC occurrence following SVR was 1.17 per 100 py (95% CI 1.11, 1.22) and 1.60 per 100 py (95% CI 1.58, 1.63) in IFN- and DAA treatment-based studies. HCC occurrence was 0.85 per 100 py (95% CI 0.85, 0.86) in the non-cirrhosis population and rose to 2.47 per 100 py (95% CI 2.42, 2.52) in the cirrhosis population. Further meta-regression analysis showed that treatment types were not associated with a higher HCC occurrence rate, while cirrhosis status was an important factor of HCC occurrence rate. CONCLUSION: HCC occurrence was significantly lower in the SVR population than in the NR population. HCC risk following SVR occurred three times more frequently in patients with cirrhosis than patients without cirrhosis. However, we found no significant difference in HCC occurrence risk following SVR between DAA and IFN therapies. CLINICAL TRIAL NUMBER: CRD42023473033.

Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

Association between polyunsaturated fatty acids and depression in women with infertility: a cross-sectional study based on the National Health and Nutrition Examination Survey.

Background: Identifying possible influencing factors is crucial for the depression symptoms of women experiencing infertility. This study aims to explore the association between polyunsaturated fatty acids (PUFAs) and the odds of depression symptoms in women experiencing infertility. Methods: This is a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). PUFA intake was obtained through a 24-h dietary recall interview. Depression symptoms were defined using the Patient Health Questionnaire-9 (PHQ-9) with a score of ≥10 points or as taking antidepressants. The association between PUFA and depression was assessed using a logistic regression model by calculating the odds ratio (OR) with 95% confidence interval (CI). Subgroup analysis was carried out based on menopausal status and female hormone use. Results: There were 725 participants included for analysis. After adjusting the covariables, lower odds of depression symptoms were found in patients with the intake of omega-3 PUFA (OR = 0.48, 95% CI: 0.24-0.96) and omega-6 PUFA (OR = 0.24, 95% CI: 0.14-0.42) in the second tertile (T2) in comparison to the first tertile (T1). The intake of α-linolenic (ALA) (OR = 0.48, 95% CI: 0.23-0.97) and linoleic acid (OR = 0.24, 95% CI: 0.14-0.41) in T2 was also found to be related to the reduced odds of depression symptoms in comparison to T1. Conclusions: Our findings suggest a potential association between moderate omega-3 and omega-6 PUFA intake and a reduced risk of depression symptoms in women experiencing infertility. This implies that clinicians might find it useful to consider dietary advice that includes PUFA-rich foods as part of a broader strategy to address mental health in this patient group. However, further research is needed to confirm these preliminary findings and to establish the optimal levels of PUFA intake for mental health benefits.

Hg2+ removal characteristics of a strain of mercury-tolerant bacteria screened from heavy metal-contaminated soil in a molybdenum-lead mining area.

In this study, the mercury-tolerant strain LTC105 was isolated from a contaminated soil sample collected from a molybdenum-lead mine in Luanchuan County, Henan Province, China. The strain was shown to be highly resistant to mercury, with a minimum inhibitory concentration (MIC) of 32 mg·L-1. After a 24-h incubation in LB medium with 10 mg·L-1 Hg2+, the removal, adsorption, and volatilization rates of Hg2+ were 97.37%, 7.3%, and 90.07%, respectively, indicating that the strain had significant influence on mercury removal. Based on the results of Fourier infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), the investigation revealed that the primary function of LTC105 was to encourage the volatilization of mercury. The LTC105 strain also showed strong tolerance to heavy metals such as Mn2+, Zn2+, and Pb2+. According to the results of the soil incubation test, the total mercury removal rate of the LTC105 inoculation increased by 16.34% when the initial mercury concentration of the soil was 100 mg·L-1 and by 62.28% when the initial mercury concentration of the soil was 50 mg·kg-1. These findings indicate that LTC105 has certain bioremediation ability for Hg-contaminated soil and is a suitable candidate strain for microbial remediation of heavy metal-contaminated soil in mining areas.

Epigenetic maintenance of adult neural stem cell quiescence in the mouse hippocampus via Setd1a.

Quiescence, a hallmark of adult neural stem cells (NSCs), is required for maintaining the NSC pool to support life-long continuous neurogenesis in the adult dentate gyrus (DG). Whether long-lasting epigenetic modifications maintain NSC quiescence over the long term in the adult DG is not well-understood. Here we show that mice with haploinsufficiency of Setd1a, a schizophrenia risk gene encoding a histone H3K4 methyltransferase, develop an enlarged DG with more dentate granule cells after young adulthood. Deletion of Setd1a specifically in quiescent NSCs in the adult DG promotes their activation and neurogenesis, which is countered by inhibition of the histone demethylase LSD1. Mechanistically, RNA-sequencing and CUT & RUN analyses of cultured quiescent adult NSCs reveal Setd1a deletion-induced transcriptional changes and many Setd1a targets, among which down-regulation of Bhlhe40 promotes quiescent NSC activation in the adult DG in vivo. Together, our study reveals a Setd1a-dependent epigenetic mechanism that sustains NSC quiescence in the adult DG.

Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study.

Purpose: Major depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them. Methods: We performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode. Results: Univariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736-1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004-1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073-1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk. Conclusion: We provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.

Double Balloon Combined with Oxytocin in Labor Induction: Analysis of Multivariate Factors Affecting the Efficacy of Cervical Ripening.

Objective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction. Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups. Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257-2.112), fetal distress (OR = 1.371, 95% CI: 1.331-2.633), and the placement of cervical ripening balloon catheter for >12h (OR = 1.563, 95% CI: 1.231-3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455-0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for >12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714-0.811). Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.

Preparation and evaluation of germanium concentrate by ultrasonic purification of tannin germanium residue.

Germanium (Ge) is a dispersed metal primarily recovered from secondary Ge-containing resources. The traditional treatment method is hindered by incomplete impurity removal, resulting in a low grade of tannin germanium residue (TGR) and Ge concentrate, high production costs, and significant hazardous waste. This study proposes a new technology involving ultrasonic pre-purification of TGR to enhance the quality of Ge concentrate prepared by roasting. Under optimal conditions (ultrasonic power 225 W, liquid-solid ratio 7:1, H2SO4 concentration 20 g/L, reaction time 30 min, and reaction temperature 40 °C), the removal efficiencies of impurities Zn, Mg, Fe, As, and S from purified tannin germanium residue (PTGR) increased by 4.2%, 4.2%, 17.4%, 8.7%, and 2.9% respectively. Moreover, the Ge content in PTGR increased from 2.9% to 4.1%. The mechanism of ultrasonic action indicated the ultrasonic energy reduced the particle size of the reactants from 67.698 µm to 31.768 µm, thereby accelerating impurity removal. Roasting ultrasonic-purified tannin germanium residue (U-PTGR) at 650 °C with 40 L/h air flow for 120 min produced Ge concentrate with a Ge grade of 33.26%, which is 6.11% higher than the regular method. Analysis using XRD and HRTEM, combined with crystallite size calculation, revealed that the Ge concentrate prepared by U-PTGR exhibited low sintering degree, good crystal properties, and high crystallinity. Implementing this technology could save enterprises approximately $57,412 annually in production costs. Additionally, it holds significant practical importance in reducing hazardous waste emissions and promoting the high-quality development of the Ge industry.

Zero-Dimensional Copper(I) Halide Microcrystals as Highly Efficient Scintillators for Flexible X-ray Imaging.

Commercially available rare-earth-doped inorganic oxide materials have been widely applied as X-ray scintillators, but the fragile characteristics, high detection limit, and harsh preparation condition seriously restrict their wide applications. Furthermore, it remains a huge challenge to realize X-ray flexible imaging technology for real-time monitoring of the curving interface of complex devices. To address these issues, we herein report two isostructural cuprous halides of zero-dimensional (0D) [AEPipz]CuX3·X·H2O (AEPipz = N-aminoethylpiperazine, X = Br and I) with controllable size to nanosize crystal as highly efficient scintillators toward flexible X-ray imaging. These cuprous halides exhibit highly efficient cyan photoluminescence and radioluminescence emissions with the highest quantum yield of 92.1% and light yield of 62,400 photons MeV-1, respectively, surpassing most of the commercially available inorganic scintillators. Meanwhile, the ultralow detection limit of 95.7 nGyair s-1 was far below the X-ray dose required for diagnosis (5.5 µGyair s-1). More significantly, the flexible film is facilely assembled with excellent foldability and high crack resistance, which further acts as a scintillation screen achieving a high spatial resolution of 17.4 lp mm-1 in X-ray imaging, demonstrating the potential application in wearable radiation radiography. The combined advantages of high light yield, low detection limit, and excellent flexibility promote these 0D cuprous halides as the most promising X-ray scintillators.

High-efficiency electrochemical nitrate reduction to ammonia via boron-doped hydroxyl oxide cobalt induced electron delocalization.

Electrochemical nitrate reduction to ammonia is a promising alternative strategy for producing valuable ammonia. This prospective route, however, is subject to a slow electrocatalytic rate, which resulted from the weak adsorption and activation of intermediate species, and the low density electron cloud of active centers. To address this issue, we developed a novel approach by doping boron into metal hydroxyl oxides to adjust the electronic structure of active centers, and consequently, led a significant improvement in the Faraday efficiency upto approaching 100 %, as well as an impressive ammonia yield upto approximately 23 mg/h mgcat-1 at -0.6 V vs. reversible hydrogen electrode (RHE). Experimental data in mechanism demonstrate that the doped boron play a crucial role in modulating the local electronic environment surrounding the active sites Co. In situ Raman and FTIR spectra provide evidences that boron facilitates the formation of deoxidation and hydrogenation intermediates. Additionally, density functional theory (DFT) calculations support the notion that boron doping enhances the adsorption capability of intermediates, reduces the reaction barrier, and facilitates the desorption of NH3.

[Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases].

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

The evaluation and enhancement strategies of core competencies for older adult caregivers in integrated medical and older adult care institutions.

The study aimed to understand the main skills of older adult caregivers and find ways to improve these skills. We selected participants using a method called random cluster sampling, where caregivers from 17 different medical and nursing care facilities across seven districts in Hangzhou were chosen. We collected 492 valid questionnaires and conducted interviews with 150 people. To analyze the data, we used T-tests and Analysis of Variance (ANOVA) to identify what factors affect caregivers' skills. We also performed multiple regression analysis to explore these factors in more depth. The analysis showed that age (p = 0.041), annual income (p < 0.001), and having a training certificate (p < 0.001) significantly influence the skills of older adult caregivers. Specifically, caregivers' age and whether they had a training certificate were linked to how competent they were, with income being a very strong factor. The study highlighted a gap between the caregivers' current skills and the skills needed for high-quality care. This gap shows the need for training programs that are specifically tailored to the caregivers' diverse needs and cultural backgrounds. Medical and eldercare facilities should adjust their work and educational programs accordingly. It's also important to look at how caregivers are paid to make sure their salary reflects their skills and the quality of care they provide. Finally, it's crucial to integrate a comprehensive training program that leads to certification within eldercare organizations.

Ferulic Acid Inhibits Arsenic-Induced Colon Injury by Improving Intestinal Barrier Function.

The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic-induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) activation and nuclear factor-kappa B (NF-κB) pathway blocking. Based on the antioxidant and anti-inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic-induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco-2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF-κB and Nrf2/HO-1 pathway in colon and Caco-2 cells were also detected. As shown in our data, FA inhibited arsenic-induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down-regulated expression of tight junction (TJ) proteins (Claudin-1, Occludin, and ZO-1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco-2 cells. In addition to suppressing the activation of NF-κB pathway, FA retrieved the activation of Nrf2/HO-1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic-induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

The Tryptophan Index Is Associated with Risk of Ischemic Stroke: A Community-Based Nested Case-Control Study.

BACKGROUND: The relative availability of the essential amino acid tryptophan in the brain, as indicated by the tryptophan index, which is the ratio of tryptophan to its competing amino acids (CAAs) in circulation, has been related to major depression. However, it remains unknown whether tryptophan availability is involved in the pathogenesis of ischemic stroke. AIMS: We aimed to investigate the relationship between the tryptophan index and the risk of ischemic stroke. METHODS: We performed a nested case-control study within a community-based cohort in eastern China over the period 2013 to 2018. The analysis included 321 cases of ischemic stroke and 321 controls matched by sex and date of birth. The plasma levels of tryptophan and CAAs, including tyrosine, valine, phenylalanine, leucine, and isoleucine, were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were employed to determine incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). RESULTS: After adjustment for body mass index, current smoking status, educational attainment, physical activity, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate, an elevated tryptophan index was significantly associated with a reduced risk of ischemic stroke in a dose-response manner (IRR, 0.76; 95% CI, 0.63-0.93, per standard deviation increment). The plasma tryptophan or CAAs were not separately associated with the risk of ischemic stroke. CONCLUSIONS: The tryptophan index was inversely associated with the risk of ischemic stroke. Our novel observations suggest that the availability of the essential amino acid tryptophan in the brain is involved in the pathogenesis of ischemic stroke.

A novel mechanism of resveratrol alleviates Toxoplasma gondii infection-induced pulmonary inflammation via inhibiting inflammasome activation.

BACKGROUND: Infection by Toxoplasma gondii can lead to severe pneumonia, with current treatments being highly inadequate. The NLRP3 inflammasome is one member of the NOD-like receptor family with a pyrin domain, which is crucial in the innate immune defense against T. gondii. Research has shown that resveratrol (RSV) prevents lung damage caused by this infection by inhibiting the T. gondii-derived heat shock protein 70/TLR4/NF-κB pathway, thus reducing the macrophage-driven inflammatory response. However, it should be mentioned that the participation of NLRP3 inflammasome in the immune response to the lung injuries caused by T. gondii infections is not entirely clear. PURPOSE: This study aims to clarify how RSV ameliorates lung damage triggered by Toxoplasma gondii infection, with a particular focus on the pathway involving TLR4, NF-κB, and the NLRP3 inflammasome. METHODS: Both in vitro and in vivo models of infection were developed by employing the RH strain of T. gondii in BALB/c mice and RAW 264.7 macrophage cell lines. The action mechanism of RSV was explored using techniques such as molecular docking, surface plasmon resonance, ELISA, Western blot, co-immunoprecipitation, and immunofluorescence staining. RESULTS: Findings indicate that the suppression of TLR4 or NF-κB impacts the levels of proteins associated with the NLRP3 inflammasome pathway. Additionally, a significant affinity for binding between RSV and NLRP3 was observed. Treatment with RSV led to a marked reduction in the activation and formation of the NLRP3 inflammasome within lung tissues and RAW 264.7 cells, alongside a decrease in IL-1ß concentrations in the bronchoalveolar lavage fluid. These outcomes align with those seen when using the NLRP3 inhibitor CY-09. Moreover, the application of CY-09 prior to RSV negated the latter's anti-inflammatory properties. CONCLUSION: Considering insights from previous research alongside the outcomes of the current investigation, it appears that the TLR4/NF-κB/NLRP3 signaling pathway emerges as a promising target for immunomodulation to alleviate lung injury from T. gondii infection. The evidence gathered in this study lays the groundwork for the continued exploration and potential future clinical deployment of RSV as a therapeutic agent with anti-Toxoplasma properties and the capability to modulate the inflammatory response.

Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

[Efficacy and safety of dust mite subcutaneous immunotherapy in children with allergic asthma： a prospective randomized controlled study]. / å°˜èž¨çš®ä¸‹å ç–«æ²»ç–—åº”ç”¨äºŽå„¿ç«¥è¿‡æ•æ€§å“®å–˜ç–—æ•ˆä¸Žå®‰å ¨æ€§çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.

Nerve growth factor alleviates arsenic-induced testicular injury by enhancing the function of Sertoli cells.

Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The pro-proliferative and anti-apoptotic effects of nerve growth factor (NGF) on SCs have been proved previously. It is still unclear whether the damage effect of arsenic on testis is related to the inhibition of NGF expression, and whether NGF can mitigate arsenic-induced testicular damage by decreasing the damage of SCs induced by arsenic. Here, the lower expression of NGF in testes of arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) was observed through detection of Western blot and Real-time PCR. Subsequently, hematoxylin and eosin (HE) staining, Evans blue staining and transmission electron microscopy were used to evaluate the pathology, BTB permeability and tight junction integrity in testes of control mice, arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) and arsenic + NGF treated mice (freely drinking water containing 15 mg/l of NaAsO2 + intraperitoneal injection with 30 µg/kg of NGF), respectively. Evidently, spermatogenic tubule epithelial cells in testis of arsenic exposed mice were disordered and the number of cell layers was reduced, accompanied by increased permeability and damaged integrity of the tight junction in BTB, but these changes were less obvious in testes of mice treated with arsenic + NGF. In addition, the sperm count, motility and malformation rate of mice treated with arsenic + NGF were also improved. On the basis of the above experiments, the viability and apoptosis of primary cultured SCs treated with arsenic (10 µM NaAsO2) or arsenic + NGF (10 µM NaAsO2 + 100 ng/mL NGF) were detected by Cell counting kit-8 (CCK8) and transferase-mediated DUTP-biotin nick end labeling (TUNEL) staining, respectively. It is found that NGF ameliorated the decline of growth activity and the increase of apoptosis in arsenic-induced SCs. This remarkable biological effect that NGF inhibited the increase of Bax expression and the decrease of Bcl-2 expression in arsenic-induced SCs was also determined by western blot and Real-time PCR. Moreover, the decrease in transmembrane resistance (TEER) and the expression of tight junction proteins ZO-1 and occludin was mitigated in SCs induced by arsenic due to NGF treatment. In conclusion, the above results confirmed that NGF could ameliorate the injury effects of arsenic on testis, which might be related to the function of NGF to inhibit arsenic-induced SCs injury.