Changes in disease burden and global inequalities in bladder, kidney and prostate cancers from 1990 to 2019: a comparative analysis based on the global burden of disease study 2019.

BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.

Neurological worsening during treatment of HIV-negative cryptococcal meningitis in a patient with Evans syndrome.

A 49-year-old woman with a rare autoimmune hematological disease, Evans syndrome, was admitted to the authors' hospital with immune reconstitution inflammatory syndrome-like reconstitution syndrome after effective antifungal therapy for cryptococcal meningitis. She initially improved after receiving corticosteroid treatment; after prednisone was tapered, her clinical presentation and brain imaging deteriorated but finally improved with the addition of thalidomide. Immune reconstitution inflammatory syndrome-like reconstitution syndrome is a rare complication in cryptococcal meningitis patients receiving immunosuppressive therapy. Thalidomide can be given in addition to corticosteroid therapy to effectively control the paradoxical inflammatory response and improve clinical outcomes.

A case report of complete remission of acute myeloid leukemia combined with DNMT3A, FLT3-TKD, and IDH2 gene mutations and active pulmonary tuberculosis treated with homeharringtonine + venetoclax + azacytidine.

In March 2022, a 58-year-old man was admitted to the local hospital for nausea and vomiting. His blood routine indicated that he had leukocytosis and anemia. The patient was diagnosed with acute myeloid leukemia (AML)-M5b accompanied by DNMT3A, FLT3-TKD, and IDH2 mutations, chest CT revealed pulmonary tuberculosis (TB). Acid-fast bacillus (AFB) was detected in sputum. The patient then received anti-TB treatment with isoniazid + rifampicin + pyrazinamide + ethambutol. On April 8, he was transferred to our hospital's Hematology Department after three consecutive negative sputum smears. He was administered the VA (Venetoclax + Azacytidine) regimen of anti-leukemia treatment and also received levofloxacin + isohydrazide + pyrazinamide + ethambutol anti-TB treatment. After one course of VA therapy, there was no remission in the bone marrow. Therefore, the patient received the HVA (Homeharringtonine + Venetoclax + Azacytidine) regimen of anti-leukemia treatment. On May 25, the bone marrow smear revealed that the original mononuclear cells were 1%. Moreover, bone marrow flow cytometry revealed the absence of any abnormal cells. mNGS showed DNMT3A (mutation rate 44.7%), but no mutations were detected in FLT3-TKD and IDH2. The patient then received the HVA regimen three consecutive times, resulting in complete remission. Repeated chest CT examinations revealed progressive regression of pulmonary TB foci, no AFB was detected in the sputum. This AML patient with DNMT3A, FLT3-TKD, and IDH2 mutations and active TB is difficult to treat. It is very necessary for him to administer prompt anti-leukemia treatment under the premise of active anti-TB treatment. The HVA regimen is effective for this patient.

Enhanced Visible-Photocatalytic Activities in Strong Acids and Strong Alkalis of Flexible Iron-SrTiO3 Nanofibrous Membranes.

Traditional SrTiO3 (STO) materials have high brittleness and poor deformation resistance. In this work, macroscopically flexible iron-doped SrTiO3 (SFTO) nanofibrous membranes were prepared by electrospinning and calcination, which can be easily isolated and can maintain integrity to recycle as photocatalysts. Moreover, the SFTO nanofibrous membranes showed enhanced photocatalytic performance under strong acids (pH = 2) and strong alkalis (pH = 12). The SFTO nanofibrous membranes increased the catalytic rate of Congo red (CR) dye by about 10 times in visible light. The mechanism of photocatalytic activity enhancement was discussed by the combined effects of hydroxyl radicals and superoxide radicals. The successful preparation of SFTO nanofibrous membranes has offered a simple and economical approach to photocatalysis as well as environmental remediation.

Activation of Atg5-dependent placental lipophagy ameliorates cadmium-induced fetal growth restriction.

Cadmium (Cd), an environmental contaminant, can result in placental non-selective autophagy activation and fetal growth restriction (FGR). However, the role of placental lipophagy, a selective autophagy, in Cd-induced FGR is unclear. This work uses case-control study, animal experiments and cultures of primary human placental trophoblast cells to explore the role of placental lipophagy in Cd-induced FGR. We found association of placental lipophagy and all-cause FGR. Meanwhile, pregnancy Cd exposure induced FGR and placental lipophgay. Inhibition of placental lipophagy by pharmacological and genetic means (Atg5-/- mice) exacerbated Cd-caused FGR. Inversely, activating of placental lipophagy relieved Cd-stimulated FGR. Subsequently, we found that activation of Atg5-dependent lipophagy degrades lipid droplets to produce free cholesterol, and promotes placental progesterone (P4) synthesis. Gestational P4 supplementation significantly reversed Cd-induced FGR. Altogether, activation of Atg5-dependent placental lipophagy ameliorates Cd-induced FGR.

The effect on brain volume in HIV-negative and non-transplant cryptococcal meningitis.

To explore the brain volume (BV) changes of HIV-negative and non-transplant cryptococcal meningitis (CM) in 1 year after initial therapy. Case data were collected from 78 CM patients who underwent magnetic resonance imaging (MRI) scanning at least 3 times in 1-year interval after initial therapy. The assessment of BV was measured by a non-commercial software, uAI Research Portal. Linear mixed model was used to investigate the association between clinical characteristics and the changes in BV. Longitudinal study showed a decrease in total brain volume (-4.65 cm3, P = .005), regional brain volume including white matter (-2.86 cm3, P = .031) and basal ganglia (-0.25 cm3, P = .007), and increase in cerebrospinal fluid (CSF) volume (3.58 cm3, P = .013) in CM patients in 1 year after initial therapy. Ventricular volume in patients with ventriculoperitoneal shunts (VPS) was lower than that in patients without VPS (-7.5 cm3, P < .05). Ventricular volume in patients with post-infectious inflammatory response syndrome (PIIRS) was larger than that in patients without PIIRS (7.1 cm3, P < .01). In addition, temporal lobe atrophy was associated with corticosteroid therapy (-6.8 cm3, P < .01). The present study suggested that brain atrophy, especially regional BV decrease, could happen in HIV-negative and non-transplant CM patients over a 1-year interval.

We investigated the evolution of brain volume changes in different regions among HIV-negative and non-transplant cryptococcal meningitis (CM) patients within 1 year after initial therapy. To assess whether brain atrophy occurs among HIV-negative and non-transplant CM patients.

Comparison of features and outcomes between HIV-negative patients with Cryptococcus gattii meningitis and Cryptococcus neoformans meningitis in South China.

OBJECTIVES: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM). METHODS: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China. RESULTS: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035). CONCLUSIONS: This study demonstrated that species identification helps to guide therapy and predict outcomes.

AtRsmD Is Required for Chloroplast Development and Chloroplast Function in Arabidopsis thaliana.

AtRsmD was recently demonstrated to be a chloroplast 16S rRNA methyltransferase (MTase) for the m2G915 modification in Arabidopsis. Here, its function of AtRsmD for chloroplast development and photosynthesis was further analyzed. The AtRsmD gene is highly expressed in green photosynthetic tissues. AtRsmD is associated with the thylakoid in chloroplasts. The atrsmd-2 mutant exhibited impaired photosynthetic efficiency in emerging leaves under normal growth conditions. A few thylakoid lamellas could be observed in the chloroplast from the atrsmd-2 mutant, and these thylakoids were loosely organized. Knockout of the AtRsmD gene had minor effects on chloroplast ribosome biogenesis and RNA loading on chloroplast ribosomes, but it reduced the amounts of chloroplast-encoded photosynthesis-related proteins in the emerging leaves, for example, D1, D2, CP43, and CP47, which reduced the accumulation of the photosynthetic complex. Nevertheless, knockout of the AtRsmD gene did not cause a general reduction in chloroplast-encoded proteins in Arabidopsis grown under normal growth conditions. Additionally, the atrsmd-2 mutant exhibited more sensitivity to lincomycin, which specifically inhibits the elongation of nascent polypeptide chains. Cold stress exacerbated the effect on chloroplast ribosome biogenesis in the atrsmd-2 mutant. All these data suggest that the AtRsmD protein plays distinct regulatory roles in chloroplast translation, which is required for chloroplast development and chloroplast function.

Clinical efficacy of laparoscopic surgery used for the excision of villus tissue and the repair of uterine scar in patients with cesarean scar pregnancy-II.

The present study described the clinical presentation of patients with cesarean scar pregnancy type II (CSP)-II diagnosed by ultrasound or magnetic resonance imaging, who underwent laparoscopic surgery resection or hysteroscopic treatment. The aim of the present study was to evaluate the outcomes of different treatments for CSP. The patients with CSP-II were assigned to the laparoscopy and hysteroscopy groups according to the type of surgery performed. The general indicators and post-operative outcomes were compared between the two groups. Statistically significant differences (P<0.05) were noted in the treatment efficacy indices between the two groups. The laparoscopic group exhibited a lower value of ß-human chorionic gonadotropin (ß-HCG) following surgery (P=0.017), a shorter time required for ß-HCG to return to normal levels (P=0.001), a reduced post-operative thickness of the uterine scar (P<0.001) and a reduced menstruation recovery time (P<0.001). However, no significant differences were noted in blood loss during operation (P>0.05). On the whole, the data indicated that the laparoscopic resection of the scar with gestational tissue and wound repair may be used to preserve the uterus and may thus be an effective method for CSP-II. The appropriate treatment needs to be selected according to the condition of each patient. Based on the latter and on the available technology, priority may perhaps be given to laparoscopic surgery.

[Extragonadal germ cell tumor: A case report and review of the literature].

OBJECTIVE: To discuss the clinical diagnosis and treatment of extragonadal germ cell tumor. METHODS: We analyzed the clinical data on a case of extragonadal germ cell tumor diagnosed and treated in the General Hospital of Eastern Theater Command and reviewed the relevant literature. RESULTS: The patient was initially diagnosed with retroperitoneal tumor and treated by resection of the tumor together with the left kidney due to the large volume of the tumor, which was complicated by pancreatic injury. Postoperative pathology showed it to be extragonadal germ cell malignancy. Postoperative examination revealed space-occupying lesion in the left testis, with serum alpha fetoprotein (AFP), human chorionicgonadotropin (hCG) and lactate dehydrogenase (LDH) negative, followed by stage-two resection of the left testis, which was pathologically shown with testicular seminoma. The patient received 7 courses of cisplatin, etoposide bleomycin (PEB) regimen and was followed up for 8 years, which found no recurrence or metastasis, and the patient fathered no child during the postoperative follow-up. CONCLUSION: For patients with a history of cryptorchidism and tumors located in the central axis, special attention should be paid to physical examination of the testes, testicular ultrasonography, and determination of AFP and other indicators to identify gonadal tumor metastasis. And if so, radiotherapy and chemotherapy can be considered first to reduce surgical complications and achieve accurate management.

[Basement membrane-related gene signature to predict biochemical recurrence in patients with prostate cancer after radical prostatectomy].

OBJECTIVE: To construct and verify a key gene signature of the basement membrane of prostate cancer (PCa) to predict the progression and biochemical recurrence of the malignancy after radical prostatectomy. METHODS: Based on the PCa-related transcriptome, gene mutation and clinical data from the Cancer Genome Atlas Project (TCGA) database, we analyzed the differentially expressed genes (DEG) related to the basement membrane in the PCa and adjacent normal prostate tissues, and subjected them to GO function enrichment and KEGG pathway enrichment analyses. We identified prognosis-related genes from the DEGs and analyzed their mutations. According to the follow-up data and biochemical recurrence after prostatectomy, we established a prognostic risk scoring model, verified its accuracy using the Gene Expression Omnibus (GEO) database, and performed survival analysis, principal component analysis (PCA), independent prognostic analysis and ROC curve analysis of the model. We constructed a protein-protein interaction network after verifying the correctness of the model by immunohistochemistry. We also established a nomogram and tested its accuracy using ROC and calibration curves. RESULTS: Totally, 85 DEGs were identified, among which 18 were up-regulated and 67 down-regulated. The prognostic risk scoring model was established with 11 of the genes. The risk of biochemical recurrence PCa was significantly higher in the high-risk than in the low-risk group (HR: 3.51, 95% CI: 2.32－5.32, P < 0.01), which was verified with the GEO database data (P < 0.01). In addition, the patients in the high-risk group were older with higher clinical T-stage, higher Gleason score, higher positive rate, larger numbers of positive lymph nodes, and a larger proportion of residual tumors than those in the low-risk group (P < 0.05). The nomogram constructed with the patients' age, pN, pT and cT stages, Gleason score and prognostic risk score manifested that the area under the ROC curve was higher than the other predictors. The calibration chart showed consistency of the predicted outcomes to the actual results. CONCLUSION: A prognostic risk scoring model of basement membrane-related genes and an effective nomogram were successfully constructed, which can predict the risk of biochemical recurrence in PCa patients after radical prostatectomy.

miR-6769b-5p targets CCND-1 to regulate proliferation in cadmium-treated placental trophoblasts: Association with the impairment of fetal growth.

Environmental cadmium (Cd) is positively associated with placental impairment and fetal growth retardation. Nevertheless, its potential mechanisms remain unclear. microRNAs (miRNAs) are known to influence placental development and fetal growth. This work was aimed to determine which miRNAs are involved in Cd-impaired placental and fetal development based on the mRNA and miRNA expression profiles analysis. As a result, gestational Cd exposure deceased fetal and placental weight, and reduced the protein level of PCNA in human and mouse placentae. Furthermore, the results of mRNA microarray showed that Cd-downregulated mRNAs were predictively correlated with several biological processes, including cell proliferation, differentiation and motility. In addition, the results of miRNA microarray and qPCR assay demonstrated that Cd significantly increased the level of miR-6769b-5p, miR-146b-5p and miR-452-5p. Integrated analysis of Cd-upregulated miRNAs predicted target genes and Cd-downregulated mRNAs found that overlapping mRNAs, such as CCND1, CDK13, RINT1 and CDC26 were also significantly associated with cell proliferation. Further experiments showed that miR-6769b-5p inhibitor, but not miR-146b-5p and miR-452-5p, markedly reversed Cd-downregulated the expression of proliferation-related mRNAs, and thereby restored Cd-decreased the proteins level of CCND1 and PCNA in human placental trophoblasts. Dual luciferase reporter assay further revealed that miR-6769b-5p directly targets CCND1. Finally, the case-control study demonstrated that increased miR-6769b-5p level and impaired cell proliferation were observed in small-for-gestational-age human placentae. In conclusion, miR-6769b-5p targets CCND-1 to regulate proliferation in Cd-treated placental trophoblasts, which is associated with the impairment of fetal growth. Our findings imply that placental miR-6769b-5p may be used as an epigenetic marker for environmental pollutants-caused fetal growth restriction and its late-onset chronic diseases.

Gestational exposure to environmental cadmium induces placental apoptosis and fetal growth restriction via Parkin-modulated MCL-1 degradation.

Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1.

Comparison on the Efficacy and Safety of Different Surgical Treatments for Benign Prostatic Hyperplasia With Volume >60 mL: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = -3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function-5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.

[Impact of high-fat diet on gene expression in mouse prostate tissue].

OBJECTIVE: To analyze the effects of high-fat diet on the biological network regulation of gene expression microarray data and key proteins in mouse prostate tissue, and provide some new theoretical evidence for the mechanism of obesity inducing PCa. METHODS: From the Gene Expression Omnibus (GEO), we obtained RNAs in the prostate tissue from two groups of C57BL / 6J mice, the normal diet group (n = 5) and high-fat diet group (n = 4). Using the Gene Cloud, Gene-Cloud of Biotechnology Informs (GCBI), GenClip2.0, and Sytoscape 3.5.1, we screened differentially expressed genes, investigated protein interaction networks and biological pathways of differential genes and, from the perspective of transcriptome, explored the effects of high-fat diet on the changes of the molecular network of prostate tissue genes and the molecular biological functions possibly involved. RESULTS: A total of 134 differentially expressed genes were identified, 130 up-regulated and 4 down-regulated, mainly involved in biological functions such as chromosome organization, cell-cell signaling, small molecule biosynthesis and leukocyte activation. The Lck, Prkcb and Cd28 genes in the gene network were of high value, indicating an important relationship with protein synthesis and biological functions, the core node of the protein-protein network, and a high predictive ability of Lck and Cd28. CONCLUSIONS: The high-fat diet can induce changes in prostate tissue genes, leading to tumorigenesis.

Global, regional, and national burden of kidney, bladder, and prostate cancers and their attributable risk factors, 1990-2019.

BACKGROUND: The burden of kidney, bladder, and prostate cancers has changed in recent decades. This study aims to investigate the global and regional burden of, and attributable risk factors for genitourinary cancers during the past 30 years. METHODS: We extracted data of kidney, bladder, and prostate cancers from the Global Burden of Disease 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and attributable risk factors from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate, age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). The associations between cancers burden and socio-demographic index (SDI) were also analyzed. RESULTS: Compared with 1990, the global incident cases in 2019 were higher by 154.78%, 123.34%, and 169.11% for kidney, bladder, and prostate cancers, respectively. During the 30-year study period, there was a downward trend in ASMR and ASDR for bladder cancer (EAPC = - 0.68 and - 0.83, respectively) and prostate cancer (EAPC = - 0.75 and - 0.71, respectively), but an upward trend for kidney cancer (EAPC = 0.35 and 0.12, respectively). Regions and countries with higher SDI had higher incidence, mortality, and DALYs for all three types of cancers. The burden of bladder and prostate cancers was mainly distributed among older men, whereas the burden of kidney cancer increased among middle-aged men. Smoking related mortality and DALYs decreased, but high body mass index (BMI) and high fasting plasma glucose (FPG) related mortality and DALYs increased among kidney, bladder, and prostate cancers during the study period. CONCLUSIONS: Kidney, bladder, and prostate cancers remain major global public health challenges, but with distinct trend for different disease entity across different regions and socioeconomic status. More proactive intervention strategies, at both the administrative and academic levels, based on the dynamic changes, are needed.

Autoimmune diseases in HIV-negative cryptococcal meningitis.

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

Gestational cadmium exposure impairs placental angiogenesis via activating GC/GR signaling.

Gestational exposure to environmental Cd caused placental angiogenesis impairment and fetal growth restriction (FGR). However, its mechanism remained unclear. This study was to investigate the effects of Cd exposure during pregnancy on placental angiogenesis and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 8 with or without melatonin (MT) (5.0 mg/kg), an anti-endoplasmic reticulum stress agent, from GD7 to GD15. Human primary placental trophoblasts and JEG-3 cells were stimulated using CdCl2 (20 µM) after MT (1 mM) preprocessing. We firstly found MT treatment obviously mitigated environmental Cd-induced placental angiogenesis disorder and reduction of the VEGF-A level. Mechanistically, MT reversed environmental Cd-downregulated the protein expression of VEGF-A via inhibiting glucocorticoid receptor (GR) activation. Notably, our data showed MT treatment antagonized Cd-activated GC/GR signaling via blocking PERK signaling and thereby upregulated VEGF-A and 11ß-HSD2 protein expression. Based upon the population case-control study, the levels of VEGF-A and 11ß-HSD2 protein in small-for-gestational-age placentae were significantly reduced when compared to appropriate-for-gestational-age placentae. Overall, environmental Cd exposure during gestation impaired placental angiogenesis via PERK-regulated GC/GR signaling in placental trophoblasts. Our findings will provide a basis for prevention and treatment of placental impairments and fetal growth restriction caused by environment toxicants in future.